bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-P09-8: ADHERENCE TO NON-PHARMACOLOGICAL MANAGEMENT AMONG HYPERTENSIVE PATIENTS
Authors: Karamulla Abbas Mohamed Ahmed , Abdelrahman Lina Saadeldin , Alnour Tanweer Elmahi , Mukhtar Shimaa Abdalla , Elhussein Shahd Salah , Elbashir Aamer Lotfi , Karamulla Jamaluddin Mohamed Ahmed
Published: January 2023

Objective:

Hypertension is a leading cause of death and disability globally, along with increasing comorbidity. It is a major public health challenge in both developing and developed countries. The non-pharmacological management is one of the most effective measures to prevent and control the hypertension, while the non-pharmacological management of hypertension includes adoption of Dietary Approach to Stop Hypertension plans (DASH), exercise, moderate alcohol consumption and smoking cessation. Nonetheless, less emphasis has been placed on the non-pharmacological management compared with treating hypertension with medication. Therefore, this study was carried out to assess the adherence to non-pharmacological management among hypertensive patients.

Design and method:

A community based cross-sectional study was conducted among 250 hypertensive patients from March to May, 2022. All adult patients (> 18 years) diagnosed with essential hypertension and met inclusion criteria were recruited. The study participants were selected using a convenient sampling technique. The data were collected by an interviewer administered standard structured questionnaire which was adopted from published literature, data were processed using the software Statistical Package for Social Science (SPSS). Binary logistic regression model (AOR, 95% CI and P- value < 0.05) was also used to determine the significant associations between dependent variables and independent variables.

Result:

A total of 250 participants, 129 (51.6%) were females, 121 (48.4%) were males, 118 (47.2%) were > 55 years old, 140 (56.0%) graduated from university and 200 (80.0%) were married. The adherence to non-pharmacological management (diet, exercise, smoking cessation and being non-alcohol consumer) percentage was 25.2%. Out of all participants; 47.6% were adherent to the diet, 46.4% were adherent to exercise, 76.4% were adherent to smoking cessation and 96.4% were non-alcohol consumers. The variables associated with adherence to diet were university education and marriage (AOR 0.30; 95% CI: 0.09- 0.92), (AOR 0.23; 95% CI: 0.06- 0.81) respectively. The variables associated with adherence to exercise were being male and no comorbidities (AOR 0.34; 95% CI: 0.18- 0.64), (AOR 1.10; 95% CI: 0.37- 3.23) respectively. The variables associated with adherence to non-pharmacological management were duration of hypertension > 20 years (AOR 3.50; 95% CI: 1.01- 12.19) and good knowledge about hypertension (AOR 0.03; 95% CI: 0.11- 0.45).

Conclusion:

The study revealed that the majority of hypertensive patients are not adherent to non-pharmacological management. Therefore, more effort should be directed to increase knowledge about non-pharmacological management and draw attention to its importance.
PS-P10-1: ARTERIAL HYPERTENSION AS A COMMON DISEASE IN ACUTE KIDNEY INJURY AND ITS SIGNIFICANT DEPENDENCE ON THE DAMAGE MECHANISM
Authors: Kwiatkowska Marlena , Kawalec Malgorzata Twardowska , Malyszko Jolanta
Published: January 2023

Objective:

Hypertension (HT) is an overwhelming finding in chronic kidney disease and but again data on hypertension prevalence in acute kidney injury-AKI are very scarce. The etiology of HT in AKI could be multifactorial and depend on the type of AKI. The aim of the study was to assess blood pressure control in patients with AKI admitted to the nephrology department.

Design and Method:

The retrospective analysis of 215 (mean age 58y) patients with AKI (N17) was made based on the medical documentation. Demographic data as well as type of hypotensive drugs, the presence of volume overload, and BP control, need for dialysis were analyzed. Among patients with AKI 35% requires acute hemodialysis-HD due to either clinical or biochemical indications. Prevalence of hypertension was 70%, with the highest in postrenal AKI- 85% followed by renal 75 and prerenal -30%

Results:

AKI patients requiring HD were significantly older than patients treated conservatively group (Me = 67 vs. Me = 54y, p < 0,01), had much higher both systolic and diastolic blood pressure values (p < 0.01 for both). The renal function was less present in AKI group requiring HD. The peripheral edema as well as pulmonary congestion was observed significantly more often in HD group with uncontrolled BP, and postrenal origin of AKI. The average number of hypotensive drugs was 5 in HD and 3 in non-HD patients. The most used hypotensive drug was calcium channel blocker, diuretic and beta-blocker.

Conclusions:

Hypertension is very common in AKI, however it depends upon the origin of AKI. Uncontrolled hypertension together with oedema and pulmonary congestion are the indications for HD initiation. However, caution should be exercised during HD to avoid hypotensive episodes.
PS-P10-8: RELATIONSHIP BETWEEN BLOOD PRESSURE AND PRESENCE OF TREATMENT FOR HYPERURICEMIA
Authors: Kuwabara Masanari , OhmotoSekine Yuki , Itoh Hidetaka , Hisatome Ichiro , Kodama Takahide
Published: January 2023

Background:

Uric acid is strongly associated with hypertension. However, it is unclear whether drug treatment for hyperuricemia decreases blood pressure or not.

Methods:

This study is a cross-sectional study using the data from 13,087 participants (4,698 female) who had annual health check-up at the Health Management Center and Diagnostic Imaging Center, Toranomon Hospital, Tokyo in 2017. We compared systolic and diastolic blood pressure between participants with and without drug therapy for hyperuricemia. Moreover, we compared systolic and diastolic blood pressure between more than 7 mg/dL and 7 mg/dL and less of serum uric acid levels in participants with drug therapy for hyperuricemia. The presence or absence of drug therapy for hyperuricemia was confirmed by questionnaire methods.

Results:

The number of hyperuricemic participants was 18 in female and 642 in male. The number of hyperuricemic female was very small, and therefore, this study analyzed only hyperuricemic male. Of the 642 male, 153 participants were hyperuricemia without drug therapy and 489 participants were hyperuricemia with drug therapy. Serum uric acid levels and systolic and diastolic blood pressure in hyperuricemic participants with drug therapy is lower than those without drug therapy (serum uric acid levels 6.23 ± 1.01 mg/dL versus 7.25 ± 1.15 mg/dL; systolic blood pressure 124.2 ± 12.4 mmHg versus 125.1 ± 13.7 mmHg; diastolic blood pressure 79.13 ± 8.83 mmHg versus 79.69 ± 8.83 mmHg), even though the drug therapy group was significantly older than absence of drug therapy group (59.7 ± 9.7 years old versus 56.8 ± 11.2 years old, p = 0.002). In the drug therapy group, those with more than 7 mg/dL of serum uric acid (N = 79) had higher systolic and diastolic blood pressure than those with 7 mg/dL and less of serum uric acid (N = 410) (systolic blood pressure 125.2 ± 11.2 mmHg versus 124.0 ± 12.7 mmHg; diastolic blood pressure 80.52 ± 8.78 mmHg versus 78.86 ± 8.48 mmHg), even though those with more than 7 mg/dL of serum uric acid were significantly younger than those with 7 mg/dL and less of serum uric acid (57.3 ± 9.8 years old versus 60.2 ± 9.6 years old, p = 0.015).

Conclusion:

Drug therapy for hyperuricemia is associated with lower systolic and diastolic blood pressure compared with absence of drug therapy for hyperuricemia. Adequate hyperuricemia control could lead to good blood pressure control. Further randomized controlled trials are desired to reveal the relationship between blood pressure and presence of treatment for hyperuricemia.
PS-R03-10: CASE REPORT: CUSHING SYNDROME IN A YOUNG MALE
Authors: Ishiga Kohei , Yoshimura Shiori , Fukuoka Akihiro , Kobayashi Ryu , Kanaoka Tomohiko , Wakui Hiromichi , Toya Yoshiyuki , Tamura Kouichi
Published: January 2023

A 27-year-old male without any significant past medical history was advised to visit a hospital for elevated blood pressure, elevated liver enzymes, and dyslipidemia in a workplace health checkup. His body weight had increased by more than 10 kg in the last two years. He presented to our department and underwent laboratory work-up. He had bilateral lower limb pitting edema, hypokalemia, and elevation of low-density lipoprotein. No sign of dysthyroidism, renin-angiotensin-aldosterone system disorder, or increased catecholamine secretion was found. Diet and exercise therapy and calcium channel blocker did not improve his hypertension, and he suffered from lumber vertebral fracture, refractory hypokalemia, and lower leg cellulitis. He was admitted to our department for detailed examination of worsening lower limb edema. On admission, he had striae on his abdomen and legs as well as edema of both lower extremities. The endocrinological data showed high levels of adrenocorticotropic hormone (ACTH) and cortisol. Overnight 1 mg dexamethasone suppression test resulted in a non-suppression response, and his circadian rhythm of cortisol was absent. Urine cortisol level was high. These findings confirmed the diagnosis of ACTH-dependent Cushing syndrome. A contrasted magnetic resonance imaging (MRI) scan demonstrated enlargement of the pituitary gland more than 1 cm in length.

Taking into account drug-resistant hypokalemia and vulnerability to infection, he was administered with metyrapone 500 mg per day until he underwent transsphenoidal hypophysectomy. The pathological findings were consistent with that of a pituitary adenoma. Postoperative MRI scan showed remnant lesions which stretch to the bilateral cavernous sinuses and the right middle cranial fossa. Although a decrease in urine cortisol was observed, the absence of a circadian rhythm of cortisol, hypertension, and hypokalemia persisted. He is now treated with somatostatin analog and craniotomy followed by gamma knife surgery is planned.

Cushing syndrome should be suspected in cases of early-onset hypertension with symptoms including weight gain, hypokalemia, and bone fracture.
PS-R04-1: A CASE OF DRUG-INDUCED RENAL INJURY AND DRUG-INDUCED HYPERTENSION RESULTING IN HYPERTENSIVE EMERGENCIES
Authors: Adachi Keika
Published: January 2023

48 years old male. He had high blood pressure for 2 years and was treated at a Chinese herbal medicine shop, the prescription was changed each time. He began to have headaches and was taking triple doses of NSAIDs daily. Three months later, he developed lightheadedness and edema. He was diagnosed with hydrocephalus, Ommaya reservoir was inserted, but his loss of consciousness was prolonged. He was transferred to the neurosurgery department of our hospital on X + 3 for close examination of the tumor. At the time of transfer, his Cr was 9.32 mg/dl and he was referred to our department. He was suspected to have uremic symptoms, so Hemodialysis (HD) was started. Renal biopsy revealed nephrosclerosis and drug-induced kidney injury (DKI). Since the previous physician had discontinued NSAIDs and Chinese herbal medicine, so we mainly managed him with antihypertensive therapy. The Neurosurgical examination was negative for tumor, and the patient was transferred to the Department of Neurology on X + 11 for further examination of encephalopathy. Although his blood pressure was 230/140 mmHg immediately after transfer, the presence of endocrine hypertension was excluded, and the symptom improved by the elimination of the uremia and lowering of the blood pressure by ARB, CCB and HD. In addition, extensive white matter lesions on head CT resolved, so he was diagnosed Posterior reversible encephalopathy syndrome (PRES). He was weaned from HD on X + 29 after his urinary output recovered, but was transferred to our department on X + 31 for decision making including reintroduction of HD because of his Cr 5.08 mg/dl level. He was discharged from the hospital on X + 47 after starting half-pulse steroid therapy (0.5 mg/kg post therapy) for DKI, with a strong desire to avoid reintroduction of HD. Currently, his Cr is 2.87 mg/dl. This case of hypertensive emergency was caused by DKI and drug-induced hypertension. NSAIDs suppress renal prostaglandin production by inhibiting COX, resulting in decreased renal function and increased blood pressure. Although the details of the Chinese herbal remedy are unknown, we suspected that NSAIDs was the cause of the hypertension, because the RAA system is usually suppressed if licorice is the cause. Although the rate of conversion from hypertensive emergencies to maintenance dialysis has not been shown, it is considered that the early release of renal load by HD in this case led to the recovery of renal function.
PS-R04-2: A CASE OF SUCCESSFUL PERCUTANEOUS TRANSLUMINAL RENAL ANGIOPLASTY (PTRA) FOR RENAL ARTERY STENOSIS ASSOCIATED WITH TAKAYASU'S ARTERITIS
Authors: Ishida Manna , Ishii Akira , Yokoi Hideki , Matsubara Takeshi , Yanagita Motoko
Published: January 2023

Introduction:

In Japan, renal vascular hypertension based on renal artery stenosis (RAS) accounts for 1% of all hypertensive patients, and RAS is present in approximately 10% of autopsy cases of coronary artery disease and cerebrovascular disease. As ischemic nephropathy and complications of cardiovascular disease (CVD) due to RAS are common, early diagnosis and treatment for RAS is important. However, results of several large clinical trials have not shown the efficacy of percutaneous transluminal renal angioplasty (PTRA) for atherosclerotic RAS.

Case:

51-year-old woman who diagnosed as Takayasu's arteritis (TA) 35 years ago, had been treated with 5 mg daily of prednisone. She presented with hypertension and edema in both legs a year before admission. Her examination at that time revealed increased serum creatinine from 1.0 to 1.7 mg/dL, high proteinuria (7.3 g/gCr), high renin activity (47.0 ng/mL/hr) and right RAS. Eight months before admission, she had an operation for ruptured descending aorta. She had recurrent episodes of dyspnea on exertion, worsening leg edema and severe hypertension and was admitted to the hospital for the treatment.

Clinical course:

In addition to severe hypertension (190/80 mmHg) and progression of RAS, she had pulmonary congestion, high brain natriuretic peptide (BNP) level (1149.5 pg/mL), increasing creatinine levels (Cr 3.1 mg/dL), and left non-functioning kidney on admission. Despite taking 8 types of antihypertensive drugs and diuretics without renin-angiotensin system inhibitors, blood pressure and fluid retention were poorly controlled, and thus we decided to perform PTRA for the right RAS. After the PTRA, edema, hypertension and pleural effusion had been dramatically improved. In addition, we could observe decrease of serum creatinine (Cr 1.6 mg/dL), proteinuria (0.5 g/gCr) and plasma renin activity (1.9 ng/mL/hr). Therefore, we reduced the antihypertensive drugs from 8 to 2.

Discussions:

Although the benefit of PTRA for RAS associated with TA remains unclear, the clinical course suggests that the success of PTRA in this case may be related to the fact that the RAS was complicated by TA. It also suggests that we should consider PTRA in cases of hypertension and pulmonary congestion associated with RAS which are difficult to control like this case.

Conclusion:

We have experienced a case of RAS associated with TA that was successfully treated with PTRA.
PS-B10-5: EFFECTS OF CHRONIC ACETYLCHOLINESTERASE INHIBITION WITH PYRIDOSTIGMINE ON CARDIOVASCULAR SYSTEM AND AUTONOMIC BALANCE IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Behuliak Michal , Bencze Michal , Boros Almos , Vavrinova Anna , Vaneckova Ivana , Zicha Josef
Published: January 2023

Objective:

The imbalance in autonomic nervous system, characterized by increased sympathetic and attenuated parasympathetic activity, plays an important role in the pathogenesis of hypertension. The spontaneously hypertensive rats (SHR) which are one of the most studied animal models of essential hypertension, are characterized by autonomic nervous system imbalance. Our study was aimed to determine the effect of chronic inhibition of acetylcholinesterase with pyridostigmine on cardiovascular parameters and sympatho-vagal balance in SHR and Wistar-Kyoto (WKY) rats.

Design and method:

Adult male SHR and WKY rats were treated with pyridostigmine (25 mg/kg/day) in drinking solution for 2 weeks. The rats were implanted with telemetric transducers to measure blood pressure (BP) and heart rate (HR). Autonomic balance was evaluated by power spectral analysis of systolic blood pressure variability (SBPV) and heart rate variability (HRV). Sympatho-vagal balance was also evaluated pharmacologically by administration of methylatropine (antagonist of muscarinic acetylcholine receptors) and propranolol (antagonist of beta-adrenergic receptors) in a separate set of rats.

Results:

SHR have elevated BP, increased vascular sympathetic activity (low frequency component of SBPV), and reduced HRV compared to WKY. Pyridostigmine significantly reduced HR in rats of both strains (during both dark and light phase) and BP during the dark (active) phase compared to untreated controls. Acetylcholinesterase activity in plasma was significantly reduced by pyridostigmine treatment in both strains (SHR 53 ± 3%, WKY 46 ± 3%). Sympatho-vagal balance examination revealed reduced cardiac vagal tone in SHR as evidenced by blunted HR response to the muscarinic receptor blocker methylatropine and increased cardiac sympathetic tone as evidenced by elevated HR response to the beta-blocker propranolol. Pyridostigmine treatment increased cardiac vagal tone and decreased cardiac sympathetic tone in SHR to the levels of untreated WKY. Moreover, pyridostigmine increased HRV and reduced low frequency component of SBPV in SHR indicating the restoration of autonomic balance. The reduction of sympathetic tone in pyridostigmine-treated rats was also evident from the reduction of plasma levels of noradrenaline. The potentiation of cardiac parasympathetic activity by pyridostigmine treatment was confirmed by the attenuation of restraint stress-induced tachycardia in both strains.

Conclusions:

Chronic stimulation of peripheral cholinergic system with pyridostigmine leads to the improvement of autonomic nervous system balance in SHR by increasing cardiac vagal tone and reducing sympathetic tone. Thus, chronic treatment with acetylcholinesterase inhibitors seems to be a promising therapeutic strategy for the restoration of autonomic balance in cardiovascular diseases.
PS-B11-1: ACETATE RESTORES CARDIAC METABOLIC FLEXIBILITY IN HIGH FAT DIET-INDUCED OBESITY THROUGH HDAC MODULATION
Authors: Olaniyi Kehinde Samuel , Atuma Chukwubueze Lucky
Published: January 2023

Objectives:

Obesity remains a global epidemic and an independent risk factor for cardiovascular disease. Histone deacetylase (HDAC) activity has been implicated to increase adipogenic differentiation and consequent increase in adiposity, which are crucial features of obesity. Short chain fatty acids (SCFAs), which are potential HDAC inhibitors have been shown to be effective for glycemic/immune modulation. However, the involvement of HDAC or ANP/BNP in obesity-associated cardiac metabolic events is inconclusive. The present study hypothesized that cardiac metabolic inflexibility is dependent on cardiac ANP/BNP alteration and HDAC activity. We further sought to investigate the therapeutic potential of SCFA, acetate in high fat diet (HFD)-induced obese rat model.

Methods:

Adult male Wistar rats were assigned into groups (n = 6/group): Control, Obese, Sodium acetate (NaAc)-treated and Obese+ NaAc-treated groups received distilled water once daily (oral gavage), 40% HFD ad libitum, 200 mg/kg NaAc once daily (oral gavage) and 40% HFD+NaAc respectively.

Results:

The treatments lasted for 12 weeks. HFD resulted in increased food intake, body weight and cardiac mass. It also caused insulin resistance and enhanced Beta-cell function, increased fasting insulin, lactate, plasma and cardiac triglyceride, total cholesterol, glycogen content, lipid peroxidation, TNF-alpha, IL-6, HDAC and cardiac troponin T and gamma-glutamyl transferase and decreased plasma and cardiac GSH with unaltered cardiac ANP and BNP. However, these alterations were averted when treated with acetate.

Conclusions:

Taken together, these results indicate that obesity induces defective cardiac metabolic flexibility, which is accompanied by elevated level of HDAC and not ANP/BNP alteration. The results also suggest that acetate ameliorates obesity-induced cardiac metabolic inflexibility by suppression of HDAC and independent of ANP/BNP modulation.
PS-B11-6: ENDOTHELIAL GHRELIN RECEPTOR INCREASE WHITE FAT WEIGHT THROUGH ACTIVATION OF MTOR-PPARGAMMA PATHWAY
Authors: Kanda Takeshi , Urai Hidenori , Azegami Atsuhiko , Takahashi Rina , Itoh Hiroshi
Published: January 2023

Ghrelin secretion from the stomach acts on peripheral tissues to cause weight gain and fat accumulation in white adipose tissue (WAT). The role of endothelial growth hormone secretagogue-receptor (GHSR) in lipid accumulation was evaluated by restoring the expression of GHSR only in the endothelial cells of GHSR-deficient mice using the Cre-LoxP system (GHSR-EC). Radioisotope (RI) -labeled H-triolein was orally administered to evaluate lipid uptake in WAT. GHSR-deficient mice had reduced RI uptake in WAT compared to control mice, and GHSR-EC mice recovered the reduced RI uptake in GHSR-deficient mice. Furthermore, the body weight and WAT weight of GHSR-deficient mice after high-fat diet loading were significantly decreased compared with control mice, but increased in GHSR-EC mice. In vitro studies, ghrelin stimulation increased the uptake of free fatty acids by GHSR-mediated activation of the mTOR pathway and increased expression of PPARgamma. From these results, ghrelin takes up lipids via endothelial GHSR and contributes to fat accumulation in white adipose tissue.
PS-B11-7: LOSS OF C3A AND C5A RECEPTORS PROMOTES ADIPOCYTE BROWNING AND ATTENUATES DIET-INDUCED OBESITY VIA ACTIVATING INOSINE/A2AR PATHWAY
Authors: Chen Xiaohui , Kong Lingrang , Gao Pingjin
Published: January 2023

Complement activation is thought to underline the pathologic progression of obesity-related metabolic disorders; however, its role in adaptive thermogenesis has scarcely been explored. Here, we identified complement C3a receptor (C3aR) and C5a receptor (C5aR) as critical switches to control adipocyte browning and energy balance. We found that loss of C3aR and C5aR in combination, more than individually, increased cold-induced adipocyte browning and attenuated diet-induced obesity. Mechanistically, loss of C3aR and C5aR increased regulatory T cells (Tregs) accumulation in the subcutaneous white adipose tissue (sWAT) during cold exposure or high fat diet (HFD). Activated Tregs produced adenosine, which was converted to inosine by adipocyte-derived adenosine deaminases (ADA). Inosine promotes adipocyte browning in a manner dependent on activating adenosine A2a receptor (A2aR). These data reveal a novel regulatory mechanism of complement in controlling adaptive thermogenesis and suggest targeting of the C3aR/C5aR pathways may represent a therapeutic strategy in treating obesity and metabolic diseases.
PS-B12-1: EPLERENONE INHIBITS UUO-INDUCED LYMPHANGIOGENESIS AND CARDIAC FIBROSIS BY ATTENUATING INFLAMMATORY INJURY
Authors: Chen Gege , Chang Yi , Yang Fan , Wang Xiangting , Shimosawa Tatsuo , Xu Qingyou
Published: January 2023

Objective:

Cardiorenal syndrome (CRS) is the leading cause of death associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD), however, the underlying mechanism of CKD-induced cardiac injury is incompletely understood. We reported that aldosterone is associated with cardiac fibrosis, and that inflammatory injury and lymphangiogenesis are involved. This pathogenic mechanism CKD-induced cardiac fibrosis still needs further investigation.

Design and method:

The unilateral ureteral obstruction (UUO) model was used to replicate the CRS type 4 model. Following induction of renal injury, the rats received eplerenone for 180-day. For in-vitro studies, we exposed human lymphatic endothelial cells (hLEC) to aldosterone and eplerenone. Changes in cardiac tissue related to lymphangiogenesis and inflammatory were analyzed in vivo. Changes in lymphangiogenesis, LEC phenotypic transformation and activation of mineralocorticoid receptor (MR)/ transforming growth factor (TGF)-beta/ vascular endothelial growth factor C (VEGFC) signaling axis involved in these changes were analyzed in vivo and in vitro.

Results:

We found that eplerenone ameliorated cardiac inflammation and fibrosis in UUO rats. Moreover, eplerenone inhibited MR activation, attenuated lyphangiogenesis and LEC phenotypic transformation, and regulated TGF-beta/CTGF/VEGFC signaling axis in vivo and in vitro. The levels of podoplanin, VEGFR-3 and VEGFC confirmed the role of lymphangiogenesis and inflammatory injury. Co-expression of LEC marker LYVE-1 and myofibroblast marker alpha-SMA validated EndMT in cardiac fibrosis. Treatment with eplerenone, clarified the role of aldosterone in UUO-induced cardiac fibrosis.

Conclusions:

We confirmed that eplerenone can alleviate UUO-induced cardiac fibrosis by inhibiting inflammation and lymphangiogenesis via MR/TGF-beta/VEGFC signaling axis. These findings provide an in-depth understanding of pathogenesis of UUO-induced cardiac injury and reveal novel therapeutic targets.
PS-B12-3: ANGIOTENSIN II CAUSED ACTIVATED DNKT CELL EXPANSION IN MESENTERIC VESSEL PERIVASCULAR ADIPOSE TISSUE OF MALE MICE
Authors: Berillo Olga , Comeau Kevin , Caillon Antoine , Leclerc Severine , Shokoples Brandon , Mahmoud Ahmad UM , Andelfinger Gregor , Paradis Pierre , Schiffrin Ernesto L
Published: January 2023

Objective:

We have demonstrated that γΔ T cells, which are an innate-like T cell subset mostly found in tissues, play a role in hypertension. We showed that angiotensin (AngII) II-induced γΔ T cell expansion in perivascular adipose tissue (PVAT), hypertension and mesenteric artery endothelial dysfunction that were blunted in mice deficient in γΔ T cells. We hypothesized that single cell RNA sequencing (scRNA-seq) would reveal γΔ T cell subpopulations in PVAT involved in hypertension, vascular injury and T cell activation.

Design and method:

Male C57BL/6J mice were infused SC or not with 490 ng/kg/min AngII for 14 days (n = 3). Hypertension was confirmed by tail cuff blood pressure measurement. Mesenteric vessels (MV) with PVAT were collected, lymph nodes removed, single cell suspension obtained, samples labeled with hashtag antibodies, T cells isolated by fluorescence-activated cell sorting, the 6 samples pooled in one tube, scRNA libraries prepared with a Chromium Next GEM Single Cell 3 Reagent Kit. Sequencing was done on an Illumina Novaseq 6000, and sequences were mapped to mouse genome mm10–2020-A, data analysed using Cell Ranger pipeline and Seurat in R. Gene ontology (GO) term enrichment analysis done by Cytoscape. Cell subpopulations were validated by flow cytometry using a BD LSR Fortessa cell analyzer and data analyzed using FlowJo software.

Results:

SBP of mice was increased in AngII (141 ± 11 mm Hg) vs sham-treated mice (108 ± 2 mm Hg). ScRNA-seq yielded 5,030 cells with 137,990 reads/cell and identified 11 T cell clusters. GO term enrichment analysis revealed that CD8+ natural killer T (NKT), NKT1, γΔ T and T regulatory cell clusters have differentially expressed genes associated with immune cell activation and stress response. Subclustering of T cells expressing the T cell receptor (TCR) Δ constant chain (Trdc) revealed 3 ΔNKT (ΔNKT0, ΔNKT1 and activated ΔNKT cells) and 3 γΔ T cell subpopulations (Trgc1low effector memory, TCR Δ variable 4+ and apoptotic γΔ T cells). AngII increased > 2-fold the frequency of activated ΔNKT cells, and decreased by 74% ΔNKT0 cells. Gene expression profiling revealed that activated ΔNKT and ΔNKT0 cells could be identified using unique markers among Trdc+ cell population, Cd28 and Sell, respectively. Flow cytometry showed that TCRΔ+CD28+Sell- T cells were 1.7-fold increased and TCRΔ+CD28-Sell+ T cells decreased by 52% in MV-PVAT of AngII vs sham-treated mice.

Conclusion:

This study identified an activated ΔNKT cell subpopulation in MV-PVAT that may play a role in AngII-induced hypertension, vascular injury and T cell activation.
PS-B12-6: OXIDIZED LDL ENHANCES AT1-GQ SIGNALING MEDIATED BY ANGIOTENSIN II THROUGH LOX-1-AT1 COMPLEX IN ADRENAL CELLS.
Authors: Jittoku Ihara , Koichi Yamamoto , Yoichi Takami , Yoichi Nozato , Hiromi Rakugi
Published: January 2023

Objectives:

Previous clinical studies have implied that dyslipidemia is associated with increase of blood pressure (BP) or the incidence of hypertension. Oxidized LDL (oxLDL), which is increased in dyslipidemia, binds to lectin-like oxLDL receptor (LOX-1), while angiotensin II (AII), which is involved in the development of hypertension, binds to AII type 1 receptor (AT1), a G protein-coupled receptor. Using vascular endothelial cells, we have shown that LOX-1 and AT1 form a complex on the plasma membrane and oxLDL activates AT1. Notably, the activation of G protein by oxLDL is partial as shown by the results that it activates Gai but not Gaq (Gq), the latter of which mediates the AII-induced BP elevation by mechanisms including the promotion of adrenal aldosterone synthesis. However, we recently found that additional treatment with oxLDL enhanced AT1-Gq signaling compared to AII alone in genetically engineered-Chinese hamster ovary cells expressing both AT1 and LOX-1. In the present study, we examined whether oxLDL enhances AII-Gq signaling in aldosterone-producing adrenal cells, in order to strengthen the hypothesis that oxLDL potentiates AII-induced aldosterone production.

Design and Methods:

H295R, human adrenal gland carcinoma cell line were treated with oxLDL, AII, or both. Gq-dependent activation of phospholipase C was quantified by measurement of inositol monophosphate (IP1) using the IP-One assay kit. When necessary, cells were pretreated with YM-254890, a Gq inhibitor or siRNA of AT1 or LOX-1. Gq-dependent activation of Ca2+ influx was quantified by measurement of intracellular Ca2+ concentrations using the Fura-2 Ca assay kit.

Results:

The IP1 assay showed that oxLDL additively increases AII-mediated IP1 production compared to AII alone. Pretreatment of Gq inhibitor or siRNA of AT1 completely abolished and siRNA of LOX-1 partially abolished the activation of AT1-Gq signaling by the combination of oxLDL and AII. In the Fura-2 Ca assay, although AII at concentrations as low as 10–11 M and oxLDL alone did not activate Ca influx, the combination of oxLDL and AII vigorously induced the phenomenon.

Conclusions:

These results suggest that oxLDL potentiates AII-Gq signaling via a pathway depending on the LOX-1-AT1 interaction in adrenal cells. Further investigation will be required to elucidate if this phenomenon contributes to enhanced production of aldosterone both in vitro and in vivo.
PS-B13-6: AMELIORATIVE EFFECT OF VERNONIA AMYGDALINA LEAVES AND PERSEA AMERICANA LEAVES AND SEEDS ON ENDOTHELIAL DYSFUNCTION PRODUCED IN PREECLAMPSIA.
Authors: Oladele Funmilola Comfort , Airadion Augustine Ikhenya , Ojo Bukola
Published: January 2023

Objective:

this study was conducted to determine the ameliorative effect of Vernonia amygdalina (Bitter Leaves), Persea americana (Avogado) Leaves and Seeds on endothelial dysfunction produced in preeclampsia.

Design and method:

Female Rats after mated with male rats and confirmed pregnant were randomly grouped into nine and induced with Lipopolysaccharide (0.1 ml per Kg body weight) at gestational day 14 except for group one which served as the normal control. Other groups were treated with low and high doses of V. amygdalina, P. americana (Leaves and Seeds) except group two that were not treated (negative control) and group three that were treated with standard drug; Aldoment (positive control). Inducement, which was stopped after four days were done concurrently with treatment. Blood pressure and urinalysis were carried out before, during and after inducement and treatment. Biomarkers of endothelial dysfunction: Nitric Oxide (NO), Endothelial Nitric Oxide Synthase (eNOS), Soluble Endoglin (sEng), Cardiac Troponin I, Creatine Kinase (CK), Triglyceride (TG) were determined in plasma while histological analysis was done on the harvested organ (heart). Data were analysed using Graph pad at significant less than 0.05.

Results:

In preeclamptic animals, there was a significant decrease in the plasma level of NO, eNOS and increase in the plasma level of sEng, Cardiac Troponin I, and TG compared with the normal control. There was no significant change in the plasma level of CK compared with the normal control animals. In addition, histopathological evaluation of cardiac muscle showed evidence of myocardiac picnotic changes and myLcytolysis compared with normal cardiac histology in the control animals. However, treatment with ethanoic extract of V. amygdalina (Bitter Leaves), P. americana (Avogado) Leaces and Seeds at high doses (200 mL per Kg body weight) significantly reverse this alterations at almost the same level with the standard drug.

Conclusions:

The present study suggest that preeclampsia is associated with endothelial dysfunction which is evident in NO, eNOS deficiencies as well as myocardiac apoptosis and this is ameliorated with supplementation of Vernonia amygdalina, Persea americana leaves and seeds. This effect is dose dependent.
PS-B13-7: AMELIORATIVE EFFECT OF VERNONIA AMYGDALINA LEAVES AND PERSEA AMERICANA LEAVES AND SEEDS ON VASCULAR INFLAMMATION GENERATED IN PREECLAMPSIA
Authors: Oladele Funmilola Comfort , Airadion Augustine Ikhenya , Ogunyemi Rachael Funmilayo
Published: January 2023

Objective:

this study was conducted to examine the ameliorative effect of Vernonia amygdalina (Bitter Leaves), Persea americana (Avogado) Leaves and Seeds on vascular inflammation generated in preeclampsia.

Design and method:

Female Rats after mated with male rats and confirmed pregnant were randomly grouped into nine and induced with Lipopolysaccharide (0.1 ml per Kg body weight) at gestational day 14 except for group one which served as the normal control. Other groups were treated with low and high doses of V. amygdalina, P. americana (Leaves and Seeds) except group two that were not treated (negative control) and group three that were treated with standard drug; Aldoment (positive control). Inducement, which was stopped after four days were done concurrently with treatment. Blood pressure and urinalysis were carried out before, during and after inducement and treatment. Biomarkers of vascular inflammation: Vascular Endothelial Growth Factor (VEGF), Tumour Necrosis Factor (TNF), Uric Acid, Total Cholesterol, Total Protein and Albumin were determined in plasma while histological analysis was done on the harvested organ (kidney). Data were analysed using Graph pad at significant less than 0.05.

Results:

In preeclamptic animals, there was a significant increase in the plasma level of Vascular Endothelial Growth Factor (VEGF), Tumour Necrosis Factor (TNF), Uric Acid, Total Cholesterol and decrease in the plasma level of Total Protein and Albumin compared with normal control. In addition, histopathological evaluation of renal tissues showed evidence of glomerular nephritis with picnotic changes in the tubular cells compared with normal glomerular and tubular component in the control animals. However, treatment with Vernonia Amygdalin, Persea Americana Leaves and Seeds ethanoic extract at high doses (200 mL per Kg body weight) significantly reverse this alterations at almost the same level with the standard drug.

Conclusions:

The present study suggest that preeclampsia is associated with vascular inflammation which is evidence in excess of Vascular Endothelial Growth Factor, Tumour Necrosis Factor, Uric Acid, Total Cholesterol and inadequate of Total Protein and Albumin as well as glomerular nephritis and this is ameliorated with supplementation of Vernonia Amygdalina, Persea Americana Leaves and Seeds. This effect is dose dependent.
PS-C29-3: CHANGE OF PANCREAS VOLUME AND GLUCOSE METABOLIC INDEX WITH THE INCREASE OF WEIGHTS: ANALYSES OF COMPREHENSIVE HEALTH CHECKUP DATA
Authors: Sunouchi Maria , Inaishi Jun , Shimizu Ryoko , Saisho Yoshifumi , Takaishi Hiromasa , Itoh Hiroshi
Published: January 2023

Objective:

Pancreas volume measured using imaging techniques has been shown to be increased in subjects with obesity and reduced in subjects with diabetes. Beta-cell mass of pancreas also was reported to be increased with obesity in autopsy samples. While, the increase in beta-cell mass of pancreas with obesity was reported to limit in Japanese autopsy studies, suggesting that Japanese have less compensatory changes of beta-cell associated with insulin resistance. Therefore, we aimed to explore the changes of pancreas volume and glucose metabolic index including beta-cell function with the increase of weights in analyses of comprehensive health checkup data.

Design and method:

We collected subjects to have the following characteristics: 1) had our health checkup between April 2014 and March 2015 at aged 20–80 years; 2) had our health checkup between April 2015 and March 2017 with an increase in body mass index (BMI) of at least 1 kg/m2 from the baseline period; 3) no diagnosis of diabetes (HbA1c < 6.5%, fasting plasma glucose < 126 mg/dl and no medication); 4) had the adequate quality in CT images to assess the pancreas volume. The pancreas was outlined by hand in each CT image and the pancreas volume was computed by summing the product of pancreas area (cm2) of each image and the CT section thickness. Homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta) were calculated as indices of insulin resistance and beta-cell function, respectively. Paired t-test was used to analyze changes in parameters.

Results:

Thirty-five subjects (29 men, mean age 59 years, mean height 167 cm, mean weight 71 kg) were included in this analysis and mean follow-up was 21 months. BMI and HOMA-IR increased significantly from the baseline (25.5 kg/m2 vs. 27.0 kg/m2, P < 0.001 and 1.58 vs. 1.89, P < 0.05). While, there were no significant change in HOMA-beta and blood pressure from the baseline (56.4 vs. 65.7 and 122/79 mmHg vs. 126/82 mmHg, all P > 0.05).

Conclusion:

The change in beta-cell function with the increase of weights and insulin resistance was modest, consistent with the change of beta-cell mass with obesity in Japanese autopsy samples. We report the change of pancreas volume evaluating with CT image in addition to these results.
PS-C30-4: ASSOCIATION OF ASSISTED REPRODUCTIVE TECHNOLOGIES WITH ARTERIAL HYPERTENSION DURING NEWBORN
Authors: Furusawa Yuri , Iwashima Satoru , Uchiyama Hiroki , Ishikawa Takamichi
Published: January 2023

In Japan, infertility treatment including assisted reproductive technologies < ART> has become common recently, accounting for 7% of ART newborns in all births. Recently, ART has been reported to induce premature vascular aging in apparently healthy children. It is unknown whether the onset of premature vascular aging begins in the newborn period. Our study was to determine whether an increased risk of premature vascular aging is associated with ART.

The study population comprised 63 newborns < median gestational age 39 weeks, and median birth weight  3050g>in the assisted conception  group and 279 newborns  in the spontaneous conception  group. The AC group was treated as follows: 29 patients with in vitro fertilization, or with intracytoplasmic sperm injection with ovulation-inducing agents , 34 with artificial insemination, and others. After confirming the closing of the patent ductus artery using echocardiography, newborns measured their peripheral systolic  and diastolic  blood pressure  values. BP measurements of newborns were performed in the left or right legs in the relaxed supine position with basically a natural sedation. At the median age of one day after birth, comparing sys and dia BP with AC and SC group, sys BP 69 and 40mmHg vs 68 and 41mmHg, there were no significant. Similarly, in the ART group, sys and dia BP was 68 and 40mmHg, with no significant differences. However, there were significant differences between maternal age, SC, AC, and ART groups, with the median of 31years, 35years, and 37years
.

We found no evidence of increased risk of premature vascular aging with ART for infertility treatment during the newborn period. Older maternity may alter affect childhood health and development. In addition, in vitro or extrauterine fertilization exposes gamete and embryo to variable physical and hormonal environments before implantation. Exposure is brief in fresh fertilizations and more prolonged in a gamete or embryo cryopreservation, and such epigenetic modifications of the environment may have downstream effects on the vascular system. The future of precision medicine guided approaches should incorporate emerging clinical factors, such as the history of ART conception in a growing proportion of the population.
PS-C30-7: THE ASSOCIATION BETWEEN INSULIN RESISTANCE AND DECLINE IN ORGAN FUNCTION IN NON-OBESE JAPANESE INDIVIDUALS
Authors: Kaneko Kenji , Hirota Ryoko Shimizu , Makino Kanako , Nagasaka Tomoaki , Kojima Daiki , Takaishi Hiromasa , Yoshino Jun , Itoh Hiroshi
Published: January 2023

Background:

Obesity-induced insulin resistance is a critical metabolic abnormality involved in the decline in various organ functions, which likely contributes to the development of serious diseases, such as type 2 diabetes, hypertension, and cardiovascular disease. However, little information is available on the association between insulin resistance and organ function in non-obese people. The major purpose of this study was to investigate the relationship between insulin resistance (estimated by the homeostasis model assessment for insulin resistance, HOMA-IR) and selected indicators of organ-specific functions in non-obese individuals.

Materials and Methods:

We analyzed data obtained from non-obese (body mass index [BMI], 18.5 to < 25 kg/m2), non-diabetic 3546 Japanese individuals (2034 men and 1512 women) who received health checkups in 2018 at Keio University Hospital. Individuals were divided into quartiles according to their HOMA-IR values. Multiple regression analysis was performed to further investigate the relationship between HOMA-IR values and organ parameters after adjustment for covariates, such as age, gender, and BMI.

Results:

Those with HOMA-IR in the highest quartile had a higher incidence of metabolic syndrome, hypertension, stroke, and chronic kidney disease. There were significant stepwise (P < 0.05) increases in metabolic syndrome indicators (BMI, visceral adipose tissue area, triglyceride, uric acid), liver enzymes (AST, ALT, γGTP, ChE), systemic inflammatory markers (white blood cell count, CRP), systolic and diastolic blood pressure, and ocular pressure, from the first quartile to fourth quartile of HOMA-IR, whereas there were stepwise decreases in HDL-C and parameters of renal function (eGFR) and pulmonary function (forced expiratory volume, vital capacity). Multiple regression analyses revealed that HOMA-IR values were significantly (P < 0.05) associated with these parameters expect eGFR even after adjusting for covariates.

Conclusion:

Our results suggest that insulin resistance is associated with decline in the function of multiple organs in non-obese, non-diabetic Japanese individuals. Further studies are required to establish cause and effect in this relationship.
PS-C30-13: GESTATIONAL HYPERTENSION AND PERIPARTUM CARDIOMYOPATHY: EPIDEMIOLOGICAL, CLINICAL AND EVOLUTIONARY PROFILE IN THE REFERENCE HOSPITALS OF YAOUNDE
Authors: Christian Ngongang Ouankou , Paturelle Jonte Mbianda Klod , Liliane Mfeukeu Kuate , Raoul Simeni Njonnou Sylvain , Ariane Owona Ngandebe Amalia , Raspail Founou Zangue Carrel , Debozard Ouankou Merimee , Patrick Menanga Alain
Published: January 2023

Background:

Peripartum cardiomyopathy (PPCM) is a primary dilated cardiomyopathy responsible for congestive heart failure that occurs in the last two months of pregnancy or during the first five months of postpartum. It is a rare pathology with unknown etiologies. Nevertheless, several etiopathogenic factors such as an history of gestational hypertension, black race, multiparity and poverty have been incriminated. However, the epidemiological and clinical data on peripartum cardiomyopathy are little known in Cameroon, thus justifying our descriptive study.

Methodology:

We carried out a prospective descriptive study over a period of six months. It was conducted in six reference hospitals in Yaounde. The study population was made of pregnant women with dyspnoea and women who had given birth with dyspnoea. Were included all pregnant or postpartum women (from the 32nd WA to the 5th months of postpartum) who had a LVEF < 45% and/or a SF < 30% associated or not with left ventricle dilation. They were placed on treatment with a follow-up over 3 months, where they had a second cardiac ultrasound to highlight the evolutionary profile.

Results:

We enrolled 10 patients from 26 women who were pregnant or had given birth and presented with dyspnoea within 6 months. The average age was 25.9 ± 4.9 years (range: 16–33 years). The average parity was 1.6 ± 1.17 (extreme 0–3). Multiparas were the most represented. The history of gestational hypertension was the main predisposing factor found (50%); followed by multiparity (30%), the notion of twin pregnancy and advanced maternal age (20%). Heart failure was the clinical expression in 60% of cases. Sinus tachycardia was constant; followed by signs of left ventricular hypertrophy and repolarization disorders on ECG assessment. The echocardiographic pattern depicted a hypokinetic dilated cardiomyopathy (mean LVEDD 61.2 ± 8.6 mm) with an average systolic function of 27.1 ± 10.6%. The main complications were acute pulmonary edema (60%), thromboembolic events including pulmonary embolism (10%), ischemic stroke (10%) and one death (10%). The treatment mostly based on the use of diuretics, ACE inhibitors, beta-blockers, Aldactone (1/3 of the patients) without forgetting the anticoagulation made with Rivaroxaban(n = 4) for some and aspirin (n = 6); and bromocriptine (initiated in 3 patients).

Conclusion:

PPCM is a cause of heart failure during pregnancy. It primarily arises during the postpartum period regardless of maternal age. It is a serious disease due to its (important morbi-mortality rate) and its complications, both hemodynamic and thromboembolic.\
PS-C30-14: A CASE OF PREECLAMPSIA DIAGNOSED BY RENAL BIOPSY
Authors: Koshida Takeo , Suzuki Hitoshi , Iwasaki Masako , Umezawa Yukako , Yoshida Maiko , Hamaguchi Sho , Fukuda Hiromitsu , Takahara Hisatsugu , Tomita Shigeki , Suzuki Yusuke
Published: January 2023

Preeclampsia is a complicat ion of pregnancy. With preeclampsia, the patients show high blood pressure and high levels of proteinuria. Preeclampsia usually begins after 20 weeks of pregnancy in women whose blood pressure had previously been in the standard range. If the patients left untreated, preeclampsia can lead to serious complications for both the mother and baby. Meanwhile, focal segmental glomerulosclerosis (FSGS) is also need to be discriminated in pregnant women with massive proteinuria.

A 32-year-old woman has not been recognized hypertension, and has never been pointed out any urinary abnormality in a medical checkup. Her blood pressure gradually increased at 30 weeks of gestation. At 34 weeks gestation, blood pressure was 180/108 mmHg with medication, and she was detected proteinuria. Even after delivery, massive proteinuria (13.7 mg/gCr) was detected without microscopic hematuria. Then, renal biopsy was performed for definitive diagnosis. Histological findings showed focal endotheliosis of the glomeruli and double contour in which are the typical histological findings for preeclampsia.

High levels of proteinuria after delivery is important index for medical treatment. Present case was diagnosed as preeclampsia by renal biopsy resulted in keep antihypertensive treatment without any immunosuppressant. The histological implication on our clinical management of preeclampsia may be profound for understanding of strict control of blood pressure during perinatal period.