bluuebunny/crossref_metadata_2025_split huggingface dataset:
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-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.