bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-B12-4: SOLUBLE (PRO)RENIN RECEPTOR LEVEL INCREASED IN A RAT MODEL OF REDUCED UTERINE PERFUSION PRESSURE
Authors: Suda Chikahito , Morimoto Satoshi , Ichihara Atsuhiro 
Published: January 2023

Objective:
The (pro)renin receptor [(P)RR)] is a multifunctional protein with roles in angiotensin II-dependent and -independent intracellular cell signaling and as an adaptor protein between the Wnt receptor complex and vacuolar proton-translocating adenosine triphosphatase. The (P)RR is cleaved from the full length (P)RR to generate soluble (P)RR [s(P)RR], reflecting the status of the tissue activity of the (P)RR. We have shown that maternal blood s(P)RR concentrations in early pregnancy are associated with increased blood pressure in late pregnancy, while higher levels of s(P)RR in cord blood in babies are at lower risk of low birth weight. We have also reported that intracellular s(P)RR is increased by hypoxia and interacts with pyruvate dehydrogenase β; subunit (PDHB) to stabilize PDHB protein and pyruvate dehydrogenase (PDH) activity in trophoblast cells, leading to our hypothesis that (P)RR may help maintain oxidative metabolism and efficient energy production during placental ischemia. In this in vivo study, we investigated effects of reduced uterine perfusion pressure (RUPP) on PDH activity and s(P)RR levels in rats.

Design and method:
RUPP was induced by placing sliver clips around the aorta above the iliac bifurcation and the bilateral uterine arcades in pregnant Sprague Dawley rats on gestational day 14 (RUPP rats). Weights of placentas and infants were measured on gestational day 21. mRNA expressions of (P)RR, hypoxia-inducible factor 1-alpha (HIF1a), and PDHB, and protein levels of HIF1a, (P)RR, s(P)RR, PDHB, lactate, and pyruvate, and activity of PDH in placentas were measured on gestational day 21.

Result:
Weight of placentas and infants were significantly decreased in RUPP rats when compared with those of sham rats. mRNA and protein levels of HIF1a were significantly higher in RUPP rats than in control sham rats, indicating that ischemia was actually induced by RUPP. mRNA levels of (P)RR and PDHB were not significantly different between the groups. The protein level of (P)RR was not significantly different between the groups while s(P)RR protein level was significantly higher in RUPP rats than in controls. Concentrations of lactate or pyruvate and PDH activity were not significantly different between the groups.

Conclusion:
PDH activity was not decreased even under the condition of placental ischemia. s(P)RR but not full length (P)RR was increased by placental ischemia. These data suggested that s(P)RR might be increased by placental ischemia to maintain mitochondrial oxidative metabolism in rats.
PS-B12-5: THE INFLUENCE OF CELLULAR AGING ON THE MOLECULES CLEARANCE THAT UNDERGO ENDOCYTOSIS VIA AN ANGIOTENSIN II TYPE 1 RECEPTOR-DEPENDENT PATHWAY.
Authors: Takahashi Toshimasa , Huang Yibin , Yamamoto Koichi , Rakugi Hiromi 
Published: January 2023

Objective:
We recently reported that ligand binding to the receptor for advanced glycation end-products (RAGE) or oxidized LDL receptor (LOX-1) activates the G protein-coupled angiotensin II (AII) type 1 receptor (AT1) via a membrane complex of the receptor (2021 Sci Rep, 2021 iScience). The intracellular events triggered by this AT1 activation include signal transduction in a G-protein-dependent pathway and endocytosis of the ligand-receptors complex in a β;-arrestin-dependent pathway. Particularly, little is known about the significance of AT1-induced endocytosis of ligands. In this study, we used amyloid β; (A β;), a known ligand for RAGE, to examine whether cell aging affects the fate of ligands undergoing AT1-dependent endocytosis.

Design and Methods:
Human unvelical vascular endothelial cell (HUVEC) and human brain microvascluar endothelial cell (HBMEC) were continuously cultured to induce replicative senescence. Fluorescent A β; (FA β;) was used to visualize cellular uptake of A β;. Fluorescence/cell number was measured after 24hour application of FA β; (F0) or after 24hour application followed by 24hour washout of FA β; (F1). Clearance of A β; was culculated by (F0-F1)/F0. Cellular aggeragation of A β; was assessed by PROTEOSTAT∨ reagent. Pretreatment with lysosomal inhibitors (Chloroquine, Bafilomycin A), siRNA knockdown of AT1, or trehalose as a lysosomal activator was used if applicable. β;galactosidase assay and real time PCR of p16 mRNA were performed to quantify cellular senescence.

Results:
In HUVECs, pretreatment with Chloroquine or Bafilomycin A markedly decreased A β; clearance. Older HUVEC with passage 12 (P12) and older HBMEC with P20 showed higher β;-galactosidase activity and p16 expression compared with younger cells with P3 and P5, respectively. Clearance of A β; was decreased in older cells compared to younger cells in both cell types. A β; aggregation was higher in older cells than younger cells in both cell types. siRNA of AT1 prominently decreased uptake and aggregation of A β; but did not influence clearance rate of Aβ; in both types of cells. Pretreatment of trehalose significantly restored clearance of Aβ; in older HBMEC.

Conclusions:
These findings indicate that cellular senescence reduces the clearance of molecules that undergo endocytosis via an AT1-dependent pathway. Further investigation will be required, but impaired lysosomal function due to aging might be involved in this mechanism.
PS-B12-9: ASTRAGALOSIDE IV INHIBITS HYDROGEN PEROXIDE-INDUCED APOPTOSIS IN H9C2 CELLS BY ATTENUATING OXIDATIVE STRESS AND MITOCHONDRIAL DAMAGE
Authors: Qi Miaomiao , Wang qiongying , Sun Runmin , Tian Li , Bai Feng , Yu Jing 
Published: January 2023

Backgrounds:
Oxidative stress and mitochondrial damage play an important role in the pathology of cardiomyocytes apoptosis. However, the effects of Astragaloside IV(As-IV) on mitochondrial function have not been uncertain. Therefore, we assumed that As-IV inhibits hydrogen peroxide-induced apoptosis in H9c2 cells by attenuating oxidative stress and mitochondrial damage.

Objectives:
To investigate the effects and mechanisms of As-IV on hydrogen peroxide-induced apoptosis in H9c2 cells.

Methods:
H9c2 cells were divided into three groups, including normal control group (cultured without intervention), hydrogen peroxidegroup (cultured with 200 μmol/L hydrogen peroxide for 2 hours), As-IV group (cultured with 100 μmol/L As-IV for 1 hour), As-IV with hydrogen peroxide group (pretreated with 100 μmol/L As-IV for 1 hour, then incubated with hydrogen peroxide for 2 hours). FITC/PI and DCFH-DA are stained to examine levels of apoptosis and ROS receptively. Levels of SOD and MDA were measured. Stained with JC-1 probe to observe the change of mitochondrial membrane potential (MMP). Western-blot was detected to analyze the expression of Drp-1.

Results 1:
The apoptosis rate of hydrogen peroxide group ((13.22 ± 3.17 vs 40.55 ± 13.74)%, P < 0.05) was significantly higher than that of control group, which was lower in As-IV with hydrogen peroxide group((23.43 ± 4.3 vs 40.55 ± 13.74) %, P < 0.05). 2. The ROS levels were higher in hydrogen peroxide group than control group((73.53 ± 5.33 vs 39.02 ± 7.90) %, P < 0.05), which were significant reduced in As-IV with hydrogen peroxide group((57.6 ± 4.63 vs 73.53 ± 5.33) %, P < 0.05) Meanwhile, the activity of MDA was increased and the activity of SOD was decreased in hydrogen peroxide group compared with that in control group((10.97 ± 0.56 vs 4.85 ± 0.55) nmol/mL, P < 0.05), ((1192.23 ± 341.59 vs 2710.95 ± 274.32)U/L, P < 0.05). Compared with hydrogen peroxide group, As-IV with hydrogen peroxide group significantly decrease the activity of MDA and increase the activity of SOD ((6.58 ± 0.79 vs 10.97 ± 0.56) nmol/mL, P < 0.05), ((1984.66 ± 188.81 vs 1192.23 ± 341.59) U/L, P < 0.05). 3. MMP was lower and the expression of Drp1 was higher in hydrogen peroxide group than that in control group ((0.31 ± 0.01 vs 1.52 ± 0.25) %, P < 0.05), ((0.86 ± 0.003 vs 0.45 ± 0.004) %, P < 0.05). Compared with hydrogen peroxide group, MMP was significantly increased and the expression of Drp1 was downregulated ((0.65 ± 0.38 vs 0.31 ± 0.01) %, P < 0.05), ((0.72 ± 0.005 vs 0.86 ± 0.003) %, P < 0.05).

Conclusions:
As-IV exerts protective effects on hydrogen peroxide-induced apoptosis by attenuating oxidative stress and mitochondrial damage.
PS-B12-12: NOVEL PATHOPHYSIOLOGICAL ROLES OF A-SYNUCLEIN IN AGE-RELATED VASCULAR ENDOTHELIAL DYSFUNCTION AND E NHANCED PERMEABILITY.
Authors: Takami Yoichi , Wang Cheng , Yamamoto Koichi , Takeya Yasushi , Nakajima Tuneo , Takeda Shuko , Nakagami Hironori , Kaneda Yasufumi , Rakugi Hiromi 
Published: January 2023

Although α-synuclein (SNCA) is a well-known pathological molecule involved in synucleinopathy in neurons, its physiological roles remain largely unknown. We reported that serum SNCA levels have a close inverse correlation with blood pressure and age, which indicates the involvement of SNCA in age-related endothelial dysfunction. Therefore, this study aimed to elucidate the molecular functions of SNCA in the endothelium.
We confirmed that SNCA was expressed in and secreted from endothelial cells (ECs). Exogenous treatment with recombinant SNCA (rSNCA) activated the Akt-eNOS axis and increased nitric oxide (NO) production in ECs. Treatment with rSNCA also suppressed TNF-α and palmitic acid induced NF-κB activation, leading to the suppression of VCAM-1 upregulation and restoration of eNOS downregulation in ECs. As for endogenous SNCA expression, replicative senescence resulted in the attenuation of SNCA expression in cultured ECs, similar to the effects of physiological aging on mice aortas. The siRNA-mediated silencing of SNCA consistently resulted in senescent phenotypes, such as eNOS downregulation, increased β; gal activity, decreased Sirt1 expression, and increased p53 expression, in ECs. Mechanistically, loss-of-function of SNCA upregulated the expression of β;-site amyloid precursor protein cleaving enzyme 1 (BACE1), which was reported to exacerbate eNOS inactivation and permeability in ECs. Addition of SNAP, NO donor, rescued the increment of BACE1, which indicated eNOS downregulation by loss-of-function of SNCA caused BECE1 increment in ECs. Ex vivo assessment of endothelial functions using aortic rings revealed impaired endothelium-dependent acetylcholine-induced relaxation in SNCA knockout (KO) mice. Furthermore, SNCA KO mice, especially those on a high fat diet, displayed elevated blood pressure compared with wild-type (WT) mice; this could be eNOS dysfunction dependent because of the lower difference caused by L NAME administration. In addition, increased depositions of immunoglobulin were found in the aortas of SNCA KO compared with those of WT mice, which indicated enhanced endothelial permeability by in vivo loss-of-function of SNCA. Thus, these results indicate that exogenous and endogenous SNCA in ECs might physiologically maintain vascular integrity, and age-related endothelial dysfunction and enhanced permeability might be partially ascribed to loss-of-function of SNCA in ECs.
PS-C28-3: EFFECTS OF THE OLMESARTAN MEDOXOMIL ON CONTROLLING HYPERTENSION AND REHABILITATION OUTCOMES FOR INPATIENTS IN THE STROKE CARE UNIT
Authors: Matsumoto Shuji , Hoei Takashi , Tojo Ryuji , Nakamura Toshihiro 
Published: January 2023

Objective:
Hypertension is the most prevalent risk factor for stroke, based on data from many studies, and has been reported in about 64% of patients with stroke. In patients with severe hypertension, chronic heart failure or history of stroke, the lower limit of cerebral blood flow autoregulation is shifted to a higher blood pressure (BP) than in healthy subjects. Furthermore, in patients with cerebrovascular disease, CBF autoregulation can be disturbed, so that the mean BP necessary to maintain a constant CBF is higher than that in healthy subjects. In the present study, we assessed the effects of the angiotensin II type 1 receptor antagonist olmesartan medoxomil on controlling hypertension and rehabilitation outcomes for hypertensive post-stroke patients in the stroke care unit.

Methods:
Inpatients of both genders, who were aged between 20 and 75 years and had hypertension and a history of a first stroke, were eligible for participation in the present study. In total, 54 patients were enrolled in the study. Research design was an open treatment trial with pre-treatment and post-treatment evaluations for 8 weeks. After screening, the patients were administered olmesartan once daily at a dose of 10 mg for the first 4 weeks of the trial. The dose was increased over the next 4 weeks if a 24-hr SBP/DBP of < 135/80mmHg was not achieved, or if reductions in the 24-hr SBP/DBP of > 10/5 mmHg were not realized. The outcome measures were the 24-h BP (ABPM), heart rate (HR), and rehabilitation outcomes (Brunnstrom stage [BRS], Barthel index [BI] and Mini-Mental State Examination [MMSE] score).

Results:
Olmesartan was well tolerated by all patients, and no complications or adverse events (severe or fatal) were observed during the eight weeks of treatment. The SBP and DBP assessed by ABPM, decreased continuously and significantly after olmesartan administration. In all subjects, the BRS of recovery from hemiplegia in the upper limb, finger, and lower limb showed a significant improvement after 8 weeks of treatment. No decreases in BRS were observed in any of the patients during the study. Also, the BI and MMSE score significantly improved after 8 weeks of treatment.

Conclusions:
Our findings confirmed that olmesartan is an effective antihypertensive drug with good tolerability. Treating hypertensive patients with a history of stroke for eight consecutive weeks with olmesartan decreased 24-hr BP, and improved rehabilitation outcomes. These findings suggest that olmesartan has beneficial effects for the hypertensive post-stroke patients in the stroke care unit.
PS-C28-9: AMBULATORY BP DERIVED SALT SENSITIVITY INDEX AS A PREDICTOR OF THE BP RESPONSE TO RENAL DENERVATION
Authors: Ashton Jonathon Sesa , Carnagarin Revathy , Nolde Janis M , Schlaich Markus 
Published: January 2023

Objective:
Renal denervation (RDN) has been consistently shown in recent sham-controlled clinical trials to reduce clinic and ambulatory blood pressure (BP). Salt sensitivity is a critical factor in hypertension pathogenesis and severity, but cumbersome to assess by gold-standard methodology. 24-hour average heart rate and mean arterial pressure dipping, taken by ambulatory blood pressure monitoring (ABPM), can stratify patients into high, moderate and low salt sensitivity index (SSI) risk categories. Here we aimed to assess whether ABPM-derived SSI risk could predict the systolic blood pressure reduction at long-term follow-up in a real-world cohort of RDN patients.

Design and Methods:
60 participants (70.0 ± 10.3 years, 76.3% male) had repeat ABPM assessment as part of a renal denervation long-term follow and compared to their pre-RDN baseline for calculating systolic BP changes. Average time since RDN was 8.7 years ± 1.09 years. Participants were stratified into low, moderate and high SSI Risk groups, respectively. MAP dipping less than 10% and heart rate (HR) greater than 70 indicated high-risk, MAP dipping greater than 10% and HR less than 70 indicated low risk. Remaining participants were classified as moderate risk. Systolic BP changes in risk groups were compared by One-way ANOVA. Multiple regression was computed for systolic BP response, baseline SBP and High SSI Risk status.

Results:
One-way ANOVA indicated a significant treatment effect (p = 0.03) between low, moderate and high salt-sensitivity index risk calculated by ABPM measures with systolic BP reduction of 9.64 ± 3.74 mmHg, 8.41 ± 3.48 mmHg, and 28.20 ± 9.55 mmHg, respectively. Baseline SBP was not significantly different between SSI Risk groups (p = 0.18), but trended upward with increasing SSI. High SSI risk independently correlated with systolic BP reduction (p = 0.02).

Conclusions:
Our preliminary investigation indicates that SSI risk may serve as a simple and easily accessible measure for prediction of the BP response to RDN. However, the influence of pharmacological therapy on these participants is an important extraneous variable requiring testing in prospective or drug-naive RDN cohorts.
PS-C29-2: AZELNIDIPINE IMPROVES INSULIN RESISTANCE IN JAPANESE HYPERTENSIVE PATIENTS WITH METABOLIC SYNDROME
Authors: Ueshiba Hajime 
Published: January 2023

Objective:
Metabolic syndrome is related with insulin resistance and the close relation between hypertension and insulin resistance has been demonstrated. On ant-hypertensive drugs, organ-protective action other than antihypertensive action is important and should be considered when we select antihypertensive drugs.
Long-acting calcium antagonists have action of improving insulin resistance other than antihypertensive action. In this study, we examined effect of improving insulin resistance in azelnidipne of long-acting calcium antagonist in Japanese hypertensive patients with metabolic syndrome.

Design and method:
This study included 25 patients (14 men and 11 women; mean age 54.6 years) of Japanese hypertensive patients with metabolic syndrome who had prior antihypertensive treatment with ARB (poor BP control with BP > 140/90 mmHg) or no treatment. These patients were given azelnidipine 16 mg/day and the following indices were measured before and 3–6 months of azelnidipine therapy to compare their variations: systolic BP, diastolic BP, heart rate, fasting plasma glucose, fasting immunoreactive insulin(F-IRI), homeostasis model assessment for insulin resistance(HOMA-R) and HbA1c.

Results:
The mean BP was 153/90 mmHg before azelnidipine therapy but significantly decreased to 137/80 mmHg after therapy. Heart rate also significantly decreased from 88bpm to 81bpm. F-IRI significantly decreased from 15.0 microIU/ml to 10.1 microIU/ml. HOMA-R significantly decreased from 3.66 to 2.40. Other parameters had no significant changes.

Conclusions:
In Japanese hypertensive patients with metabolic syndrome who had prior antihypertensive treatment with ARB (poor BP control) or no treatment, azelnidipine therapy significantly decreased BP and heart rate and improved insulin resistance. It is speculated that this phenomenon is caused by azelnidipine effect of inhibiting the sympathetic nervous system. This study showed that azelnidipine therapy is useful for hypertensive patients with metabolic syndrome.
PS-C30-12: IMPACT OF SARS-COV-2 INFECTION TO RISK AND SEVERITY OF HYPERTENSION IN PREGNANCY AND ITS OUTCOME TO THE NEW BORN
Authors: Pradnyaandara I Gusti Bagus Mulia Agung , Winata I Gde Sastra , Putra I Wayan Artana 
Published: January 2023

Objective:
To determine relationship of SARS-CoV-2 infection to the risk and severity of preeclampsia, as well as its impact on newborns.

Design and method:
We performed a systematic search in databases (PubMed, ScienceDirect, ProQuest, and Cochrane Library) for studies examining impact of SARS-CoV-2 infection on pregnancy. Included studies were evaluated for risk of bias based on the Newcastle Ottawa Score. A meta-analysis was conducted using the data extracted from each study. Review Manager (RevMan) 5.4 was utilized to compute the summary of odds ratios (OR), mean differences (MD), and 95% confidence intervals (CI) for the outcomes. Our outcomes of interest are preeclampsia, preeclampsia with severe features, eclampsia, fetal distress and still birth. The other outcomes are preterm birth (< 37 week), instrumental labor, sectio caesaria and birth defect.

Results:
We identified twenty two observational studies involving 1,025,048 pregnancy patients. Based on the analysis, SARS-CoV-2 infection in pregnancy significantly increased the risk of preeclampsia [OR 2.01(95% CI 1.59–2.53; p < 0.00001; I2 = 82%)], and the severity was based on the high prevalence of preeclampsia with severe features [OR 3.04(95% CI 1.19–7.78; p = 0.02; I2 = 91%)] and eclampsia [OR 17.73(95% CI 13.83–22.72;p < 0.00001; I2 = 0%)]. Poor outcome in newborns in terms of incidence of preterm birth [OR 1.65(95% CI 1.54–1.76; p < 0.00001; I2 = 86%)], fetal distress [OR 19.18(95% CI 17.14–21.45; p < 0.00001; I2 = 99%)] and still birth [OR 2.12(95% CI 1.74–2.59; p < 0.00001; I2 = 0%)], were also significantly associated with SARS-CoV-2 infection.

Conclusions:
SARS-CoV-2 infection during pregnancy increases the risk and severity of preeclampsia and gives a poor outcome in newborn.
PS-C33-9: PSYCHOLOGICAL ABNORMALITIES IN PATIENTS WITH RESISTANT HYPERTENSION FOUND NON-ADHERENT BY DIRECTLY OBSERVED TREATMENT INTAKE
Authors: Polonia Jorge J , Barbosa Loide , Silva Jose Alberto , Salgueiro Andre 
Published: January 2023

Introduction & aim:
We intend to assess the underlying psychological and behavioural factors in patients with resistant hypertension (HTres) confirmed as non-adherents by directly observed treatment intake (DOTI).

Methods:
We studied with DOTI 68 patients with HTres in outpatient hypertension clinic. 24-h ambulatory BP (ABP) was evaluated before the procedure. In DOTI patients took all medications in the morning for 5 days under the supervision of a technician and performing on the fifth day a second ABP. In some patients a third ABP measurement was repeated 3–6 months after DOTI. All patients responded to appropriate questionnaires evaluating their psychological and behavioural profiles

Results:
Out of the 68 patients 76% were female and 21% diabetics in average ageing 62 years and BMI 30 Kg/m2. Average antihypertensive agents was 4.6 ± 1.2 drugs/day. After DOTI casual, daytime and night-time BP decreased significantly (24 h from 149/82 + 13/13 to 131/74 + 13/9 mm Hg, p < 0.01). Pts (n = 36, i.e. 52.9%) were classified as non-adherents (false HTres) since after DOTI vs previous 24-h ABP there was a significant reduction of mean 24 h BP to < 130/80 mm Hg or a reduction of both 24 h SBP and 24 h DBP by > 10%). Non-adherents i.e false HTres showed significant worse values of disbelief in the potential benefits of treatment, expression of emotions, hostility, anxiety, paranoid ideation, self-blame, physical mobility, smoking habits and social isolation.

Conclusions:
DOTI can be a valuable tool to identify the non-adherence to therapy as a cause of HRes. Non-adherence was associate with worse psychological and behaviour profiles.