bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAG-SACA-1: NUTRITIONAL RISK FACTORS IN SACA REGION
Authors: Patil Mansi 
Published: January 2023

One of the key factors influencing the development of hypertension is diet. As a result of its continuing rise in prevalence, HIV is the leading cause of mortality and the burden of disease worldwide. The prevalence of hypertension has rapidly increased in Iran, Pakistan, Thailand, Sri Lanka, the Philippines, China, India, and Nepal. Aging populations and negative changes in risk variables, such as tobacco use, low physical activity, and bad food, notably high salt consumption in this region, are risk factors for hypertension. It is well known that certain nutrients and foods, such as salt, potassium, fibre, and certain fruits and vegetables, have an impact on blood pressure (BP), but less is known about the impact of other nutrients and foods, particularly magnesium, calcium, dairy products, and nuts. Epidemiological data on the connections between nutrition and hypertension are plentiful, but frequently come from cross-sectional rather than prospective analyses, the latter of which have been carried out in particular populations that are likely to be comparable in terms of socioeconomic status and health consciousness. Various eating trends labelled “traditional,” “meat,” “Western,” and “prudent” have been found in studies of Asian communities. Despite the fact that the individuals who live in these countries are remarkably diverse, there are parallels in their societal structure.
In China, dietary patterns with high meat and dairy intakes have been linked to obesity, but in Thailand, a more conventional diet high in carbohydrates has been linked to metabolic syndrome. In that situation, primary dietary prevention has advanced to combat the hypertension epidemic and preventive interventions from a public health perspective are urgently needed.
PS-B01-4: ANGIOTENSIN II TYPE1 RECEPTOR INHIBITION IMPROVES VASCULAR SENESCENCE THROUGH IMPROVEMENT OF MITOCHONDRIAL QUALITY CONTROL VIA CRAF/MEK/ERK PATHWAY
Authors: Uchikado Yoshihiro , Ikeda Yoshiyuki , Uebo Shota , Sasaki Yuichi , Akasaki Yuichi , Ohishi Mitsuru 
Published: January 2023

Introduction:
Prevention of atherosclerotic cardiovascular disease has a problem of residual risk that is insufficient even if lipids are properly lowered by drugs such as statin. It has been reported that lectin-like oxidized low-density lipoprotein scavenger receptor-1 (LOX-1) associated with Angiotensin II Type 1 Receptor (AT1R). Mitochondria play crucial role in vascular senescence and atherosclerosis. We hypothesized receptor association with LOX-1 and AT1R might be a breakthrough to solve residual risk in terms of mitochondrial quality control.

Methods:
We performed in vitro and in vivo experiments using vascular smooth muscle cell (VSMC), C57BL6 (WT) and apolipoprotein E deficient (ApoE KO) mice.

Results:
Administration of ox-LDL to VSMC induced mitochondrial dysfunction and cellular senescence accompanied by excessive mitochondrial fission through Drp1 activation. This Drp1 activation was derived from the activation of CRAF/MEK/ERK pathway, which is a downstream of AT1R. AT1R inhibition inactivated ox-LDL-mediated Drp1 activation and retarded mitochondrial dysfunction, excessive mitochondrial fission and cellular senescence, indicating that LDL receptor LOX-1 associates with AT1R and activates CRAF/MEK/ERK/Drp1, leading to induction of mitochondrial fission and resulting in facilitating cellular senescence. AT1R inhibition also induced mitophagy assessed by electron microscopy and immunohistochemistry of LAMP2 and TOMM20. AT1R inhibition-induced mitophagy was not affected by Atg7 knockdown, whereas it was diminished by Rab9 knockdown. Immunohistochemistry showed TOMM20 dots were co-localized to LAMP2 and Rab9 but not LC3. These results suggest that AT1R signal induces mitophagy derived from Rab9-dependent alternative autophagy. Moreover, inhibition of either CRAF or MEK also decreased excessive mitochondrial fission and induced mitophagy, suggesting that AT1R signal followed by CRAF/MEK pathway modulates both mitochondrial dynamics and mitophagy. Taken together, inhibition of AT1R induces dual modification of mitochondrial dynamics and mitophagy through inactivation of CRAF/MEK/ERK axis. Finally, we confirmed that the degree of vascular senescence and the number of fragmented mitochondria were higher in ApoE KO than those of WT mice, and treatment with Candesartan to ApoE KO inhibited vascular senescence through induction of mitophagy and imbalance of mitochondrial dynamics.

Conclusion:
Receptor association of LOX-1 with AT1R plays a crucial role in cellular/vascular senescence induced by ox-LDL, and AT1R inhibition improves mitochondrial quality control through regulation of mitochondrial dynamics and mitophagy derived from Rab9-dependent alternative autophagy.
PS-B01-7: VASCULAR SMOOTH MUSCLE CELL NOX5 REGULATES FIBROBLAST PHENOTYPIC SWITCH AND CARDIOVASCULAR FIBROSIS
Authors: Montezano Augusto , Rios Francisco J , Blaikie Zachariel , Saad Tomador EK , Camargo Livia , Ramirez Roberto Palacios , Tarjus Antoine , Sagan Agnieszka , Beattie Wendy , Guzik Thomasz J , Jaisser Frederic , Graham Delyth , Touyz Rhian M 
Published: January 2023

Objective:
We previously observed that mice expressing human Nox5 (hNox5) in VSMC exhibit vascular dysfunction and cardio-renal fibrosis, where mechanisms are unknown. Here we postulated that VSMC-Nox5 promotes fibroblast phenotypic changes leading to myofibroblast differentiation and pro-fibrotic responses.

Design and Methods:
Fibroblasts were cultured from wildtype (WT) and hNOX5 mice (Nox5 + SM22 +). Mice (20 weeks old) were infused with Ang II (600 ng/Kg/day) for 28 days and renal fibrosis/inflammation studied. Markers of myofibroblasts, pro-fibrotic and inflammatory phenotypes were assessed by qPCR and immunoblotting.

Results:
Fibroblasts from Nox5 + SM22 + mice exhibited increased mRNA of pro-fibrotic markers, such as Col1A1 (2-ddC:1.74 ± 0.16 vs. WT 0.67 ± 0.11), Col3A1 (2-ddC:1.74 ± 0.18 vs. WT 0.96 ± 0.24) and TIMP3 (2-ddC:2.65 ± 0.25 vs. WT 0.38 ± 0.07), p < 0.05. Myofibroblast phenotype (SMC) markers mRNA, aSMA (2-ddC:1.54 ± 0.05 vs. WT 0.78 ± 0.17) and Myocd (2-ddC:1.36 ± 0.17 vs. WT 0.39 ± 0.22) were also increased, p < 0.05. mRNA expression of CD36 (2-ddC:1.37 ± 0.07 vs. WT 86 ± 0.24), TNFa (2-ddC:1.32 ± 0.2 vs. WT 0.71 ± 0.17) and TNFR1 (2-ddC:1.26 ± 0.04 vs. WT 1.02 ± 0.10) were increased, while CD68 expression was decreased (2-ddC:0.82 ± 0.11 vs. WT 1.36 ± 0.18) in fibroblasts from Nox5+SM22+ mice (p < 0.05). In Nox5 mice fibroblasts, ROS production and TGFb protein expression (AU:1.8 ± 0.05 vs. WT 1.4 ± 0.06), as well as TGFbR2 gene expression (2-ddC:2.04 ± 0.17 vs. WT 0.57 ± 0.12), were increased (p < 0.05). Kidneys from Ang II-infused Nox5+SM22+ mice exhibited significant perivascular fibrosis and inflammatory cell infiltration compared to WT. Kidney expression of vimentin (AU:1.01 ± 0.05 vs WT 0.85 ± 0.03) and aSMA (AU:0.44 ± 0.03 vs WT 0.33 ± 0.01), markers of myofibroblast differentiation, were increased in Nox5 mice (p < 0.05). Gene expression of DNMT3a and TET2, DNA methylation regulatory enzymes, were also increased in fibroblasts from Nox5+SM22+ mice, p < 0.05.

Conclusion:
VSMC-Nox5 regulates fibroblast phenotypic switch leading to fibrosis; a process that may involve increased production of ROS and TGFb, and activation of DNA methylation pathways.
PS-B01-12: SEXUAL DIMORPHISM OF CEREBROVASCULAR NOX5-NOTCH3 SIGNALLING IN ANGIOTENSIN II-INDUCED HYPERTENSION
Authors: Blaikie Zachariel S L , Montezano Augusto C , Miller Alyson A , Touyz Rhian M , Work Lorraine M 
Published: January 2023

Objectives:
NOX5 is a pro-contractile NOX isoform associated with vascular dysfunction. We demonstrated that vascular NOX5 expression is increased in cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL), a small vessel disease of the brain. CADASIL is caused by mutations in NOTCH3 and abnormal NOTCH3 signalling. Here we questioned whether cerebrovascular NOX5 influences NOTCH3 in male and female hypertensive mice.

Design and method:
Brain tissues from angiotensin II (Ang II) male and female 20-week wild-type (WT) ice and mice expressing human Nox5 (hNOX5) specifically in VSMCs studied. Ang II was administered by mini-pump (600ng/Kg/per day) for 28 days to induce a hypertension. Protein and mRNA expression of NOX isoforms and NOTCH3 (full-length and intracellular domain (ICD)) and downstream signalling of NOTCH3-specific genes were assessed using qPCR and immunoblotting respectively. Markers of oxidative stress were measured by Amplex-red and TBARS-MDA.

Results:
Ang II induced a significant increase in blood pressure in WT and hNOX5 mice. Expression of full length NOTCH3 expression was significantly increased in male Ang II-treated hNOX5 mice (AU: 0.15 ± 0.01 vs. un-treated hNOX5 0.07 ± 0.02) and unchanged in females. NOTCH3-ICD was significantly increased in male Ang II-treated WT versus WT controls (0.1 ± 0.01 untreated WT vs. 0.25 ± 0.05 Ang II WT), but unchanged in male hNOX5 mice. NOTCH3-ICD expression was unaltered in female untreated versus Ang II treated WT and hNOX5 mice. Downstream NOTCH3 gene HEY1 mRNA expression was significantly reduced in male Ang II-treated hNOX5 mice compared to untreated hNOX5 males (3.91 ± 0.3 vs. male hNOX5 untreated 2.78 ± 0.13). Irreversible protein tyrosine phosphatases (PTP-ox) were significantly increased in Ang II-treated hNOX5 mice (AU: 4.91 ± 0.6 vs. 2.18 ± 0.14) and was unchanged in hNOX5 female mice. MDA lipid peroxidation markers were decreased in female hNOX5 Ang II-treated mice (umol/protein: 1.28 ± 0.26 vs. hNOX5 3.25 ± 0.43), but not males. NOX5 induced no changes in NOX1-4 protein expression, or ROS measures in males or females.

Conclusions:
Ang II-induced hypertension in VSMC-specific NOX5 mice leads abnormal NOTCH3 signalling, downstream HEY1 transcription, and increased PTP-ox in a sex-dependent manner. In conclusion, in brains from VSMC-specific hNOX5 mice under a hypertensive phenotype, NOTCH3 expression is increased with associated attenuation of NOTCH3 downstream gene expression and increased PTP signalling. These findings were only evident in male mice. Our data suggest a possible relationship between NOTCH3 signalling and NOX5 that seems to be sex-specific. Implications of this sexual dimorphism await further clarification in the context of hypertension and vascular dysfunction.
PS-B02-5: NICORANDIL SUPPRESSES ISCHEMIA-INDUCED CARDIAC NOREPINEPHRINE ENHANCEMENT AND VENTRICULAR ARRHYTHMIAS IN PRESSURE OVERLOAD-INDUCED HYPERTROPHIC HEARTS.
Authors: Kobara Miyuki , Amano Toshihiro , Toba Hiroe , Nakata Tetsuo 
Published: January 2023

Objective:
Ventricular arrhythmias are a common cause of sudden death in acute myocardial infarction (MI) and hypertension is a major risk factor of MI. Nicorandil, an ATP sensitive potassium channel (KATP) opener, is usually used in the treatment of acute MI. KATP expresses in nerve terminals as well as cardiomyocytes and KATP in nerve terminals regulates norepinephrine release. The effects of nicorandil on ischemic myocyte are fully defined. On the other hand, the roles of nicorandil on ischemic norepinephrine release in hypertrophic cardiac tissue has remained unexplored. We examined whether nicorandil suppressed interstitial norepinephrine level and ventricular arrhythmia during acute ischemia in chronic pressure overload-induced hypertrophic hearts.

Design and Methods:
Rats were divided into two groups: abdominal aortic constriction (AAC) group and sham-operated (Sham) group. Four weeks after constriction, cardiac geometry and function were examined using echocardiography and hemodynamic measurements, and cardiac tissues were stained with hematoxylin and eosin and Sirius Red for histological examinations. In other rats, 4 weeks after constriction myocardial ischemia was induced by the left anterior descending artery occlusion for 100 minutes in the presence or absence of intravenous infusion of nicorandil. Cardiac interstitial norepinephrine concentration in ischemic region was measured using the microdialysis method. Ventricular arrhythmias were monitered by ECG during whole ischemic period.

Results:
Four weeks after constriction, remarkable left ventricular wall thickening and diastolic dysfunction were observed in AAC group. In histological examination, remarkable myocyte hypertrophy and interstitial fibrosis were observed in AAC group. Before ischemia, ventricular arrhythmia was not found in both groups. Number of ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation, was increased in early ischemic period (−20 min) in both groups, and was grater in AAC group. Before ischemia, interstitial norepinephrine concentration in cardiac tissue was higher level in AAC group than in Sham group, and ischemia increased norepinephrine concentration in both groups. Nicorandil administration in ischemic period significantly suppressed the number of ventricular arrhythmias and abolished the ventricular tachycardia and fibrillation without hemodynamic alterations in hypertrophic hearts. Nicorandil also attenuated epinephrine enhancement in acute ischemic period in hypertrophic hearts.

Conclusion:
Ischemia-induced ventricular arrhythmias were more frequent and severe in hypertrophic hearts and associated with high interstitial norepinephrine concentration. Nicorandil suppressed ischemia-induced interstitial norepinephrine release by neuronal KATP opening, which attenuated ventricular arrhythmias in pressure overload-induced hypertrophic hearts.
PS-C01-1: CARDIOVASCULAR EVENTS PREDICTION RELATED TO AGE IN PATIENTS WITH HYPERTENSIVE CRISES IN 12-MONTHS FOLLOW-UP GREEK STUDY
Authors: Fragoulis Christos , Dimitriadis Kyriakos , Polyzos Dimitrios , Mavroudis Andreas , Leontsinis Ioannis , Kariori Maria , Kakouri Niki , Kouremeti Maria , Andrikou Ioannis , Grigoriou Kalliopi , Thomopoulos Costas , Konstantinidis Dimitrios , Tsioufis Konstantinos 
Published: January 2023

Objective:
Few data have been published regarding the long-term prognosis of patients with hypertensive crises (hC). The aim of our study was to record the prevalence and clinical phenotype of patients with hypertensive urgencies (hU) and emergencies (hE) assessed in the emergency department (ED) and during hospitalization and a 12-month follow-up to record new events in a Greek tertiary hospital.

Design and method:
The registry population consisted of patients admitted to the ED with acute increase in blood pressure (BP) (systolic BP > or = 180mmHg and/or diastolic BP > or = 120mmHg) and depending on the presence or absence of acute hypertension-mediated target organ damage they were divided into the HE and the HU group, respectively. In all patients the demographic and clinical parameters were recorded for 12 months and there was a 12-month follow-up for new end points.

Results:
Out of 38,589 patients assessed in the ED during a period of 12 months, 353(0.91%) had hC, out of whom 256(72.5%) had HU and 97(27.5%) had hE. The mean age of all patients was 67.4 ± 12.9 years, 49% were males and 80% had a history of hypertension. During the study period 81 patients were excluded for not completing the follow-up. We stratified the total population of hC by age separating patients into two groups, e.g. > or = 65 and < 65 years old, and analyzed the composite end point consisting of deaths or hospitalizations caused by cardiovascular disease. Patients > or = 65years old presented more composite events (36 vs 8 events, p = 0.019, hR for patients > or = 65years 2.68, 95% CI 1.18–6.12). Cox regression models were adjusted for age, gender, cardiovascular disease, chronic kidney disease and diabetes mellitus.

Conclusions:
Our study implies that age > or = 65years is an independent risk factor for deaths or hospitalizations caused by cardiovascular disease in patients with hC. There is an arising necessity for more intensive follow-up of these patients and the need for further research in this setting.
PS-C01-12: EARLY DETECTION OF DEMENTIA USING AI-BASED EYE-TRACKING TECHNOLOGY
Authors: Takeda Shuko , Oyama Akane , Nakajima Tsuneo , Ito Yuki , Takami Yoichi , Takeya Yasushi , Yamamoto Koichi , Sugimoto Ken , Rakugi Hiromi , Morishita Ryuichi 
Published: January 2023

Responding to the rapid rise in the number of dementia cases is becoming increasingly urgent. A great deal of evidence indicates that early diagnosis and timely intervention lead to beneficial outcomes. Vascular risk factors such as hypertension can be a potential target for dementia prevention as controlling blood pressure can reduce the risk of developing dementia later in life. A diagnostic method for the easy and accurate detection of mild symptoms of dementia is necessary to provide early intervention. Neuropsychological tests, such as the Mini-Mental State Examination (MMSE), are commonly used as a screening tool to detect cognitive impairment. These traditional neuropsychological tests are valid and reliable; however, they are not sufficiently simple and rapid as routine screening tools.
Here, we developed a newly developed eye tracking-based cognitive assessment tool to detect cognitive impairment. The gaze points of the subjects were recorded by the eye-tracking device while a series of short (178 s) task movies are displayed on the monitor, and the cognitive scores are determined from the gaze plots data. Eighty participants, including 27 cognitively healthy controls (HC), 26 patients with mild cognitive impairment (MCI), and 27 patients with dementia, were assessed by both an eye tracking-based and neuropsychological tests. A strong positive correlation was observed between the MMSE and eye tracking-based cognitive scores (r = 0.74, p < 0.00001, Spearman rank test). The eye tracking-based cognitive scores also correlated well with other neuropsychological tests such as FAB and ADAS-cog, and they also demonstrated a good diagnostic performance in detecting MCI.
Eye tracking-based cognitive assessment provides a new platform for a quantitative scoring and sensitive detection of cognitive impairment. Furthermore, we developed an easy-to-administer cognitive assessment application for smart devices such as iPad. This will facilitate early intervention, leading to the prevention of dementia. We are currently conducting a medical device clinical trial in Japan and preparing for the global extension of this service.
PS-C02-3: GREATER BLOOD PRESSURE VARIABILITY MEASURED BY 24-HOUR AMBULATORY BLOOD PRESSURE MONITORING PREDICTS THE RECURRENCE AFTER ATRIAL FIBRILLATION CATHETER ABLATION
Authors: Hayashi Hiroya , Ito Asahiro , Toyoda Natsumi , Yanagishita Tomoya , Ito Ayaka , T Kim Andrew , Nakatsuji Kenichi , Ogawa Mana , Ishikawa Sera , Yoshiyama Tomotaka , Iwata Shinichi , Izumiya Yasuhiro , Fukuda Daiju 
Published: January 2023

Objective:
Atrial fibrillation (AF) is an important prognostic factor even in the general population, and its clinical importance is increasing with the aging of the population. In recent years, catheter ablation (CA) of AF has become a common treatment modality, but recurrence of AF is observed in some patients. Especially, hypertension is an important risk factor for recurrence of AF after CA. Regarding blood pressure measurement, ambulatory blood pressure monitoring (ABPM) is known to provide a better prediction of cardiovascular events compared to conventional clinical BP measurement. However, the association between ambulatory BP variables (BPV) and AF recurrence after CA remains unclear. The purpose pf this study is to identify the association between BPV measured by 24-Hour ABPM device and recurrence after CA for AF.

Design and method:
All patients were admitted in Osaka metropolitan university hospital to undergo CA of AF, and were measured 24-hour BP monitoring using an ambulatory BP device (Mobil-O-Graph) after CA between August 2017 and April 2021. Twenty four-hour mean peripheral and central systolic/diastolic BP were separately calculated. BPV was calculated as coefficient of variation (standard deviation/mean BP).

Results:
A total of 107 patients were included in this study. After a median follow-up period of 563 days, AF recurrence was documented in 23 of 107 patients (21.5%). In univariate analysis, patients with AF recurrence tended to have higher age (OR = 1.08, 95%CI = 1.02–1.14, p < 0.01), serum BNP (OR = 1.00, 95%CI = 1.00–1.01, p = 0.01), CHADs2 VASc score (OR = 1.67, 95%CI = 1.22–2.29, p < 0.01), left atrial volume index (OR = 1.07, 95%CI = 1.04–1.10, p < 0.01), E/e’ (OR = 1.11, 95%CI = 1.02–1.21, p = 0.02) than those of non-AF recurrence. In ABPM variables, greater 24-hour mean peripheral and central systolic/diastolic BPV were associated with AF recurrence after CA, whereas any indices of 24-hour mean BP variables were not (Table 1.). Multivariate cox regression analysis after adjustment for relevant variables, 24-hour mean peripheral and central systolic/diastolic BPV were independently associated with AF recurrence after CA (Table 1.).

Conclusions:
Greater BPV measured by ABPM, either in peripheral or central, were indicated to be predictors of AF recurrence after CA. Our data suggest that BP control to aim at minimizing BPV attenuates the risk of AF recurrence after CA.
PS-C03-8: NOVEL STUDY TO SEE ARTERIAL STIFFNESS CHANGES WITH POSTURE IN HYPERTENSIVE SUBJECTS IN ASIAN POPULATION
Authors: Sule Ashish Anil , Cesar Benedict A , Cangco Noe M 
Published: January 2023

Aim:
To see the effect of postural variation on parameters of arterial stiffness, in Asian population especially in Singapore.

Methods:
Postural variations and their effects on measures of arterial stiffness were analysed in 2 groups of patients consisting of hypertensive subjects (57 patients) and normotensive subjects (54 patients). Operator index (OI), central pressures such as aortic systolic pressure (ASP), aortic pulse pressure (APP), Aortic Pulse Augmentation (APA), Augmentation Index (AI) and brachial blood pressures (BP) such as brachial systolic pressure (SP) and brachial diastolic pressure (DP) were measured in supine and sitting positions. Differences between BP characteristics in supine and sitting were compared using non parametric paired test of Wilcoxon Signed-rank test. A p-value of p < 0.05 was accepted as statistically significant

Results:
A statistically significant increase in APP (45(35–54) vs 42(31–48) = 0.0058 and a significant decrease in DP (75(69–83) vs 78(69–87), p = 0.023) was seen in the supine position as compared to in the sitting position. A similar trend of significant increase in APP and decrease in DP (33(28.3–36) vs 30(23.3–33.8), p = 0.00158 and 62(55–67) vs 65(59–71), p = 0.0006 respectively was seen in normotensive subjects.

Conclusion:
Postural changes has an effect on arterial stiffness. Normotensive subjects and hypertensive patients on treatment behave similarly on postural changes. On the other hand, hypertensive subjects who are not on medications, behave differently with posture. Central aortic pulse pressure is a sensitive marker for postural variation response of arterial stiffness.