bluuebunny/crossref_metadata_2025_split huggingface dataset:
AW-NI-6: MINERALOCORTICOID RECEPTOR ACTIVATION LEADS TO HIGH BLOOD PRESSURE DUE TO BODY POTASSIUM AND WATER LOSS
Authors: Minegishi Shintaro , Morisawa Norihiko , Kitada Kento , Wild Johannes , Keat Yam Wan , Han Hong Yu , Marton Adriana , Minegishi Kaoru , Tiing Lim Tzy , Ishigami Tomoaki , Tamura Kouichi , Nishiyama Akira , Kovalik Jean Paul , Titze Jens 
Published: January 2023

Objective:
Mineralocorticoid receptor (MR) activation is known to reduce renal Na+ elimination and increase body fluid, resulting in arterial hypertension. We have reported earlier that high salt intake, chronic renal failure and psoriasis occur blood pressure increases initiated by body water loss. Here we tested the hypothesis that DOCA treatment induces a similar adaptive water conservation response that also causes arterial hypertension.

Design and method:
Male C57BL/6J mice on the low-salt diet (<0.1% NaCl) were divided into four groups: tap water (control), tap water with subcutaneous 25 mg DOCA (DOCA), 1% NaCl water with DOCA (DOCA salt), 1.44% NaHCO3 water with DOCA (DOCA NaBic). We performed continuous metabolic cage studies. Na+, K+, and water were measured in mice tissue by desiccation and consecutive dry ashing. Blood pressure was measured by telemetry. We also studied body composition, glucocorticoid-receptor (GR) protein/chromatin interaction, skin blood flow perfusion and renal vascular resistance. Metabolome and key enzyme activities of energy production in kidney, skeletal muscle and in liver were compared between four groups.

Results:
Compared to control mice, DOCA mice showed increased urine volume, lower urine osmolality and increased blood pressure. DOCA salt developed arterial hypertension within 3 days of the experiment (P < 0.001, Fig. 1A). In DOCA salt mice, K+ and water loss occurs in the initiation phase of arterial hypertension (Fig. 1B), indicating solute and water loss from the intracellular space. Further water loss was then prevented by secondary Na+ accumulation, indicating that the initial MR-driven dehydration reverted back to normal body fluid level by means of Na+ accumulation. Additional physiological adaptation to DOCA salt-driven body water loss included increased vascular resistance (Fig. 1C) and catabolic amino acid breakdown (Fig. 1D). DOCA NaBic mice showed similar massive primary K+ loss and secondary Na+ retention, but no arterial hypertension occurred (Fig. 1A). While DOCA salt decreased skin blood flow, DOCA NaBic increased it (Fig. 1C). DOCA salt mice showed renal glutamine catabolism as well as muscle protein catabolism (Fig. 1D). This catabolic state was coupled with glucocorticoid receptor binding in skeletal muscle.

Conclusions:
DOCA salt leads to pronounced initial K+ and water loss with hypertension. Na+ retention occurs only secondarily and is a compensatory response that reverts initial body water loss back to normal body water levels. Additional NaBic feeding reveals that the blood pressure level in mice with MR activation is determined by changes in blood flow independent of body Na+ or water content.
JS-IC: AGREEMENT REGARDING OVERCOMING HYPERTENSION IN THE ASIAN HYPERTENSION SOCIETY NETWORK 2022
Authors: JSH International Committee  
Published: January 2023

Within Asia, religions and cultures differ, and economic development differs from region to region. However, despite this diversity, things will not progress efficiently or in a certain direction unless certain rules are in place. The global burden of hypertension has already been acknowledged. The reduction in blood pressure significantly reduces cardiovascular morbidity and mortality. Half of the world's population is concentrated in Asia, and this proportion is expected to continue to increase. As the population ages, the number of people suffering from hypertension is also expected to increase. It is critical to address hypertension in Asia. To do so, it is necessary to establish a common direction for the control of hypertension within the Asian region.
Since last year, Japanese Society of Hypertension has performed meeting and discussion with 14 Asian countries/regions to conquer hypertension in Asia. In this session, we will present the agreement to overcome hypertension in Asian population, and representatives from each country/region will make comments. In addition, this agreement will be published in Hypertension Research on the same day.
JS-WHL-ISH-RTSL-3: IS THE CURRENT RECOMMENDATION BY GUIDELINES FOR HYPERTENSION TO KEEP DAILY SODIUM INTAKE BELOW 5 G (SODIUM 2300 MG) REALISTIC?
Authors: Whelton Paul Kieran 
Published: January 2023

The human kidney has an exquisite ability to regulate sodium. Absent kidney disease or drugs that interfere with sodium transport, humans require little dietary sodium for physiological function. Most natural foods are low in sodium content. Generally, higher sodium intakes result from the consumption of processed foods or foods that contain excess sodium that has been added during food preparation.
Policy recommendations for dietary sodium reduction are in place in almost 100 countries but the specifics of what is recommended and the approaches to implementation of the recommendations vary substantially. Daily sodium intake targets vary from about 1,200 to 2,400 mgs/day. A recent treatment trials dose-response meta-analysis identified a direct linear relationship between sodium intake and blood pressure (BP), suggesting that any reduction in dietary sodium intake is beneficial for BP lowering.
Feeding studies have demonstrated a capacity to substantially reduce sodium intake. This approach can be applied in commercial programs but has only modest generalizability as a clinical or public health approach. Feeding studies do, however, underscore the value of policies aimed at reducing the addition of sodium during food processing and food preparation. Large behavior-change trials with relatively long periods of follow-up have documented 20–30% reductions in sodium intake. Sodium intake reductions of 10–20% have been achieved in national programs, with the degree of success depending on the level of rigor for implementation of sodium reduction strategies.
Collectively, experience indicates that reducing sodium intake is challenging, especially over prolonged periods of follow-up. However, it can be achieved in both the clinical and public health setting, and even modest reductions in sodium intake result in important health benefits.
JS-HR-10: ADVANCES IN RENAL DENERVATION FOR TREATING HYPERTENSION
Authors: Katsurada Kenichi 
Published: January 2023

Excessive activation of sympathetic nervous system is closely related to the onset and progression of hypertension. Renal nerves are composed of sympathetic efferent and sensory afferent nerves. Activation of the efferent renal sympathetic nerves induces renin secretion, sodium absorption, and increased renal vascular resistance, which lead to increased blood pressure (BP) and fluid retention. Afferent renal sensory nerves, which are densely innervated in the renal pelvic wall, project to the cardiovascular center in the brain to modulate sympathetic outflow to the periphery, including the heart, kidneys, and arterioles. Renal denervation (RDN) is a neuromodulation therapy that partially interrupts both the efferent outputs from the brain to the kidney and the afferent inputs from the kidney to the brain and has attracted attention as a novel device therapy for hypertension. In clinical practice, denervation is performed through the lumen of the renal artery using a catheter. Radiofrequency, ultrasound, and alcohol-based RDN devices are being developed as new second-generation devices. A randomized sham-controlled trials using 24-hour ambulatory BP measurement is required for approval of clinical use of RDN. The SPYRAL HTN OFF-MED pivotal trial showed the superiority of RDN using radiofrequency-based catheter compared with a sham procedure to safely lower 24-hour systolic BP in the absence of antihypertensive medications. The RADIANCE-HTN TRIO trials showed the superiority of RDN using ultrasound-based catheter compared with a sham procedure to safely lower daytime BP in patients with resistant hypertension. The REQUIRE trial is the first trial of ultrasound RDN in Asian patients from Japan and South Korea with resistant hypertension.
The study findings were neutral for the primary endpoint, with similar reductions in 24-hour systolic BP in the RDN and sham control groups. Although BP reduction after RDN was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. Japanese Society of Hypertension performed the meta-analysis of nine randomized sham-controlled trials of RDN including these three trials mentioned above. The results showed that RDN significantly reduced a range of office, home and 24-hour BP parameters in patients with resistant, uncontrolled, and drug-naïve hypertension. There were no significant differences in magnitude of BP reduction between radiofrequency-based and ultrasound-based devices. Recently, the efficacy and safety of RDN in the SPYRAL HTN OFF-MED pivotal trial up to 36 months have been reported. In this session, the latest basic and clinical evidence/aspects of RDN will be summarized and discussed, which is about to be introduced into the clinical practice.
RAG-SACA-3: ROLE OF PRIMARY CARE PHYSICIAN TO MANAGE HYPERTENSION IN A LOW-RESOURCE SETTING
Authors: Barua Lingkan 
Published: January 2023

Hypertension is a primary care clinical condition that is therefore best detected, managed, and followed at a primary care level by a primary care team led by a physician. However, the delivery of primary care services is not unique in all countries, especially in low- or lower-middle-income countries where primary care physicians used to manage hypertension in low-resource settings (LRS). This presentation will focus on the concept of LRS, a list of potential roles played by a primary care physician, and possible challenges usually face. Usually, the settings where health care systems do not meet the minimum standards set by the World Health Organization or any other quasigovernmental organization are considered LRS. However, there is no explicit definition for LRS. The major roles of a primary care physician in LRS are identification of an individual at high risk for HTN, proper screening, diagnosis with a proper communication strategy to inform about the diagnosis, cost-effective rational treatment with counseling, and finally follow-up. The primary care physician is at the heart of a team-based HTN care in an LRS and will provide supportive supervision to the team to ensure the best outcome: (i) increased patient enrollment, (ii) increased patient treatment rate, (iii) improve BP control rate, (iv) high treatment compliance (v) reduction of drug stock-outs. In LRS, without team-based care and shifting of tasks, it will be very difficult to ensure proper management.
In general, a primary care physician will play a leadership role in a resource-poor setting to successfully implement an HTN management program.
PS-B01-3: IS IT POSSIBLE TO ACCELERATE SENESCENCE IN THE VASCULAR ENDOTHELIAL CELL BY MODULATING SEVERAL MICRORNAS?
Authors: Toyama Kensuke , Spin Joshua M , Tsao Philip S , Mogi Masaki 
Published: January 2023

Backgrounds:
Many factors are involved in cellular aging, and senescence induction requires complex regulation of various signaling networks and processes. Specifically, in the area of aging-related vascular cognitive impairment, laboratory-based findings have not yet yielded agents of practical use for clinical settings. One possible reason is that the physiologic elements of aging have been insufficiently considered such as in a drug screening experiments (particular in the vitro-blood brain barrier model). It is difficult to age primary human cerebral vascular endothelial cells for the experiments using standard methods because of their limited ability to survive in vitro. To establish techniques to mimic cellular aging by modulation of microRNAs, we aimed to identify key microRNAs capable of fine-tuning aging-associated genes, and thereby regulating the senescence of vascular endothelial cells.

Methods:
To identify candidate microRNAs, expression microRNA array was performed between control and senescent vascular endothelial cells. Thereafter, bioinformatic analysis was used to select key microRNAs. These candidates were then modulated in vitro using microRNA mimics and inhibitors in vascular endothelial cells, and senescence-associated gene expression patterns were evaluated by qPCR.

Results:
Seventeen microRNAs were significantly increased more than 2-fold in senescent cells. Of those, bioinformatic analysis concluded that miR-181a-5p, miR-30a-5p, miR-30a-3p, miR-100-5p, miR-21-5p, and miR-382-5p were likely associated with regulation of cellular senescence. We evaluated the potential targets of these six microRNAs by comparing them with cell-cycling and apoptosis-related genes from published mRNA transcriptional array data from aged tissues, and found that miR-181a-5p, miR-30a-5p and miR-30a-3p were enriched in overlapping targets compared with the other candidates. When modulating and comparing these microRNAs in vascular endothelial cells with several patterns, we noticed that over-expression of miR-30a-5p, and inhibition of both miR-30a-3p and miR-181a-5p, induce senescence.

Conclusion:
Simultaneous upregulation of miR-30a-5p, and downregulation of both miR-30a-3p and miR-181a-5p, mimic cellular senescence in vascular endothelial cells. This single step induction, as opposed to the time-consuming process of replicative passage senescence, would be useful for mimicking cell senescence vitro model.
PS-B01-5: TISSUE-SPECIFIC REGULATION OF LRG1 EXPRESSION IN MULTIPLE HYPERTENSION MODELS OF MOUSE
Authors: Miyazawa Tomohito , Okami Naohito , Yukawa Naoki , Tsukamoto Shunichiro , Tanaka Shohei , Azushima Kengo , Wakui Hiromichi , Tamura Kouichi 
Published: January 2023

Object:
Leucine-rich alpha-2-glycoprotein-1 (LRG1), which is firstly isolated from human plasma, has been reported to be related to several diseases as a biomarker or a pathogenic factor. Serum LRG1 is associated with the prognosis of diabetic nephropathy and cardiovascular diseases, and we previously demonstrated that LRG1 especially plays a pivotal role in the initial development of diabetic nephropathy. In addition, a previous study showed that increased plasma LRG1 levels in patients with type 2 diabetes mellitus was associated with increased systolic blood pressure (BP), arterial stiffness estimated by pulse wave velocity, and decreased endothelium-dependent vasodilation estimated by laser doppler flowmetry. However, the relationship between LRG1 and BP have remained substantially unknown.
With respect to the function of LRG1, LRG1 is expressed in endothelial cells and promotes pathological angiogenesis by modulating TGF-beta signaling. LRG1 switches TGF-beta signaling from the Smad2/3 pathway to the Smad1/5/8 pathway. In addition, the activation of Smad2/3 signaling enhanced endothelial nitric oxide synthase (eNOS) production and promoted endothelium-dependent vasodilation. Suppressing eNOS activity reduces NO levels and leads to endothelial dysfunction and hypertension. Moreover, LRG1 is increased in response to inflammation and oxidative stress in endothelial cells. However, little is known about the relationship between LRG1 in endothelial cells and eNOS.
Based on the previous findings, we hypothesized that LRG1 may inhibit eNOS production by potentially blocking the Smad2/3 pathway, which will promote to form a vicious cycle that progresses vascular endothelial damage and hypertension. As the first step to elucidate this hypothesis, we investigated LRG1 expression in various tissues including vascular endothelium in some hypertension models with endothelial dysfunction.

Design and method:
Male 10–12 weeks-aged C57/BL mice were divided into control and hypertension with endothelial dysfunction. BP was measured using a tail-cuff method during the experiment, and mice were sacrificed and their organs were collected at the end of the experiment. We examined the expression of LRG1, Smad2/3, Smad1/5/8 and NOS in the vascular endothelium, kidney, heart, adipose tissue by PCR, Western blot and immunohistochemical analyses.

Results:
We are currently conducting the experiments and will present our findings at this conference.

Conclusion:
We plan to present the results of tissue-specific regulation of LRG1 expression in some hypertension models of mice at this conference.
PS-B01-8: MALAYSIAN TUALANG HONEY INHIBITS PDGF-INDUCED HUMAN VASCULAR SMOOTH MUSCLE CELLS PROLIFERATION AND MIGRATION
Authors: Azman Ain Nabila Syahira Shamsol , Yong Yoke Keong 
Published: January 2023

Introduction and Objective:
Cardiovascular diseases (CVD) are the leading cause of death globally. Atherosclerosis is a common CVD which can lead to the deadliest heart failure. Increasing evidence showed that abnormal vascular smooth muscle cells (VSMC) proliferation and migration constitute the main pathological basis of atherosclerosis. These events are potently stimulated by platelet-derived growth factor (PDGF), causing phenotypic switching of VSMC from a mature, quiescent phenotype to a proliferative, migratory phenotype which is commonly observed in the development of atherosclerosis. Furthermore, study have revealed that PDGF elevates the concentration of reactive oxygen species (ROS) which stimulates VSMC proliferation and migration. Pharmacological treatment for atherosclerosis is often an ongoing, long-term regimen that may have adverse effect to an individual. Thus, alternative therapy based on natural products can potentially be the frontier in atherosclerosis treatment. Interestingly, previous study revealed that Malaysian Tualang Honey (MTH) is capable of protecting vascular endothelial cells from inflammation. However, little is known on the effect of MTH on the PDGF-induced VSMC proliferation and migration. Therefore, the present study aimed to determine the antioxidant, anti-proliferative and anti-migratory effects of MTH in PDGF-induced VSMC.

Methodology:
VSMC were treated with increasing concentrations of MTH (0.001–10%) for 24 hours and the cell viability were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were then be treated with non-cytotoxic concentrations of MTH and induced with 20ng/mL PDGF for 72 hours to determine the proliferation rate via MTT assay. The intracellular ROS were measured in these cultured cells by dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Wound healing assay were used to determine the anti-migration activities on PDGF-induced VSMC treated with MTH.

Results:
Our data showed that MTH concentrations ranging from 0.01% to 1.00% showed no cytotoxic effect to VSMC. Co-culture of the cells with MTH significantly inhibits the proliferation and migration of PDGF-stimulated VSMC in a concentration-dependent manner. Pre-treatment of cells with MTH prior to culturing in 20ng/mL PDGF showed a significant decrease in the production of ROS.

Conclusion:
This study demonstrates that MTH inhibits VSMC proliferation and migration by suppressing the production of ROS which constitute the pharmacological basis of anti-atherosclerotic action. Therefore, MTH potentially can be a promising therapeutic agent in the treatment of atherosclerosis.
PS-B02-15: LIGHT POLLUTION, OBESITY, AND HYPERTENSION- “LIFESTYLE” RISK FACTORS ASSOCIATED WITH AN INCREASED RISK OF MALIGNANT ARRHYTHMIAS. ANTIARRHYTHMIC EFFECT OF OMACOR.
Authors: Sykora Matus , Benova Tamara Egan , Zurmanova Jitka , Knezl Vladimir , Tribulova Narcis , Bacova Barbara Szeiffova 
Published: January 2023

Objective:
Light pollution disrupts circadian rhythms that may promote obesity and hypertension, but their association with the susceptibility to malignant cardiac arrhythmias is not well known. We examined whether continuous light as well as a high sucrose diet affect rat heart gene transcripts, miRNAs, or protein expression and hence arrhythmogenesis. In parallel, the benefit of omega-3 (Omacor) supplementation was assessed.

Design and method:
In the first experiment, male and female spontaneously hypertensive (SHR) and normotensive Wistar (WR) rats were housed in 12 h/12 h light/dark cycles or exposed to continuous light at 300 lux for 6 weeks. In the second experiment, aged female WR rats were fed with 30% sucrose for 8 weeks. In both experiments half of the rats were supplemented with Omacor (200 mg /100 g b.w). Susceptibility to electrically-inducible ventricular fibrillation (VF) was assessed in perfused heart.

Results:
Rats exposed to continuous light or fed by sucrose were more vulnerable to develop VF. There was a down-regulation of myocardial connexin-43 (Cx43) along with an increased pro-inflammatory NF-kB and iNOS transcripts and decreased sarcoplasmic reticulum Ca2+ ATPase transcripts in response to continuous light. Omacor treatment increased the electrical threshold for VF induction associated with attenuation of pro-arrhythmic alterations in myocardial Cx43, NF-kB and iNOS.
Sucrose fed rats exhibited suppression of Cx43 and PKC epsilon signaling, along with upregulation of myocardial PKC delta and miR-30a that is involved in fibrosis. Myocardial miR-1 expression levels involved in the regulation of Cx43 were not affected by the sucrose diet nor Omacor treatment. Antiarrhythmic effects of Omacor supplementation have been shown by attenuation of Cx43, PKC, and miR-30a myocardial abnormalities.

Conclusions:
Findings suggest that light pollution and sucrose diet jeopardize myocardial Cx43-mediated electrical communication, thereby increase susceptibility of the heart to malignant arrhythmias. Adverse effects were alleviated by treatment with Omacor, supporting its potential benefit and the relevance of monitoring the omega-3 index in at-risk human populations.
This research was supported by VEGA 2/0002/20, 2/0158/19, APVV 21-0410, 18-0548, 19-0317, EU ITMS 26230120009
PS-C01-4: ASSOCIATIONS OF ARTERIAL STIFFNESS ONSET AGE WITH TYPE 2 DIABETES RISK: A LARGE-SCALE CHINESE COHORT STUDY
Authors: Li Fei , Zhu Liyong , Yang Yiping , Wang Jie , Wu Jingjing , Miao Rujia , Cai Jingjing , Yuan Hong , Lu Yao 
Published: January 2023

Objective:
To explore the associations between arterial stiffness (AS) onset age and type 2 diabetes (T2DM) risk.

Design and Method:
This study enrolled 22,588 participants free of T2DM at baseline. All participants take an annual physical examination from 2012 to 2016, with fasting blood glucose and brachial-ankle pulse wave velocity measurements. Cox proportional model was used to investigate the association between AS onset age and T2DM risk. Sex specific analysis was also performed, as well as examining the association between early vascular aging (EVA), normal vascular aging (NVA), supernormal vascular aging (SUPERNOVA) onset age, and diabetes risk.

Results:
Totalling 757 (3.4%) participants were diagnosed with T2DM. Compared with participants free of AS in each specific age group, the earlier AS onset age was more strongly associated with T2DM risk, especially for the middle age, with the fully adjusted hazard risk (HR) and 95% confidence interval (CI) of 4.63 (2.79, 7.67) for AS onset age at 50. Similar results were observed both in males and females, with the fully adjusted HR and 95% CI of 4.54 (2.60, 7.93) for males and 4.86 (1.48, 16.01) for females, with AS onset age at 50. Such association was also observed in the exploration of EVA, NVA, and SUPERNOVA onset age and incident T2DM risk.

Conclusions:
This study revealed that middle-aged onset of AS was more significantly associated with a higher risk of T2DM. Early screening of AS, especially in middle age, may assist in T2DM detection and postpone diabetic vascular complications developing.