bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-P03-10: SETTING UP OF MYWASSH, THE MALAYSIAN SOCIETY FOR WORLD ACTION ON SALT, SUGAR AND HEALTH: PROMOTE SALT REDUCTION IN MALAYSIA
Authors: Chia Yook Chin , Chung Felicia Fei Lei , Ooi Pei Boon , Chew Ming Tsuey , Cheng Daniel Maoung Hui
Published: January 2023

In response to non-communicable diseases in particular cardiovascular diseases being the leading cause of premature deaths in high as well as middle income countries, the World Health Organisation in 2013, proposed several targets to address this problem. One of the targets set was reduction of salt intake to less than 5gm per day by 2030 - to reduce the prevalence of hypertension.

Salt intake is of particular importance because intake of salt in Asia is high, ranging from 9–17 gm/day. Furthermore, high salt intake is more important in Asia as salt sensitivity is higher in Asians causing a rise greater rise in blood pressure (BP) compared to Caucasians. Furthermore, the impact of BP in Asians is again higher than in Caucasians, making it even more important to reduce BP as much as possible.

Reduction in salt intake needs a multi-prong, multi-sectorial approach. One strategy to help reduce salt intake is public education. We cannot rely only on the government and health authorities alone to ensure the reduction of intake of salt. To this end, a group of interested health care professionals, dietitians, scientists got together to set the society to help educate the public. This society was successfully formed and registered under the Malaysian Registrar of Societies in November 2021 and launched by the Deputy Minister of Health Malaysia in May 2022. A website was also created and language specific educational materials including videos were created by the members themselves.

To strengthen the Society activities and aligned with international organisations, the society sought and was granted affiliated membership with the World Hypertension League and the

International Society of Hypertension. A memorandum of understanding was signed with UK WASSH and Sunway University (SU) as SU is very much committed to UN Sustainable Development Goals - health is one the arms and willing to provide a lot of support for our educational activities. Furthermore, a monetary grant was successfully secured to help defray expenditure related to our educational activities.

We need more salt warriors- i.e., the people who will help educate the public, food vendors, the food manufacturers and lobby public policy as well. The young and enthusiastic members have already embarked educational activities at various sites throughout the country. We believe the efforts of this new Society will have impact and by sharing this, we hope other countries in Asia will also start the battle against a high salt intake.
PS-P04-9: PULSE PRESSURE AND MEAN ARTERIAL PRESSURE IN HYPERTENSIVES WITH MULTI-MORBIDITY: AN ANALYSIS USING GLOBAL DATA FROM MAY MEASUREMENT MONTH (MMM)
Authors: Wang Wei , Janssen Carolina , Schlaich Markus , Schutte Aletta E , Stergiou George , Poulter Neil R , Beaney Thomas
Published: January 2023

Background:

The increasing prevalence of people living with multimorbidity is an increasing challenge for health systems. Mean arterial pressure (MAP) serves as the steady component in a patient's arteries during one cardiac cycle while pulse pressure (PP) is recognized as the pulsatile component. Along with systolic blood pressure (BP) and diastolic BP, both MAP and PP are established risk factors for the development of major adverse cardiovascular events. The knowledge of how PP and MAP vary among hypertensives according to the presence of one or more long-term conditions (LTCs) is limited. May Measurement Month (MMM) is the largest contemporary global BP screening campaign designed to raise awareness of high BP.

Purpose:

To identify the association between BP parameters and number of LTCs (diabetes, myocardial infarction and stroke) in participants with hypertension.

Design and methods:

MMM is an opportunistic cross-sectional survey with over 4.8 million volunteers aged over 18 years recruited between 2017–2019, and 2021 in 106 countries. Three sitting BP readings were taken for each participant on a single occasion, with data on demographics, lifestyle, hypertension and LTCs collected. Hypertension was defined as systolic BP greater than 140mmHg and/or diastolic BP greater than 90mmHg (average of the second and third readings) and/or taking antihypertensive medication(s). Mixed-effects linear regression models were applied to compare the BP parameters with different numbers of LTCs, assuming random intercepts for country to account for clustering. Multivariable models were adjusted for age and sex (with an interaction term), medication use, current smoking and alcohol consumption.

Findings:

We analysed data from 1,107,432 individuals with hypertension, recorded data on LTCs and with all three BP readings. Overall, 860,376 (77.7%) had no LTCs, 188,306 (17.0%) had one, 40,592 (3.7%) had two, and 18,158 (1.6%) had three LTCs. After adjustment for potential confounders, the average PP of hypertensives without LTCs was 52.9mmHg. Compared to those with no LTCs, the PPs were significantly higher at 54.4mmHg, 54.9mmHg, and 53.6mmHg, in hypertensives with one, two or three LTCs, respectively (all p < 0.001). A strong inverse relationship was seen between MAP and numbers of LTCs, with mean MAPs of 104.1mmHg, 103.8mmHg, and 101.5mmHg in those with one, two or three LTCs respectively, compared to participants without (104.4 mmHg) (all p < 0.001).

Conclusion:

Our study highlights that the presence of one or more LTCs is associated with higher PP and lower MAP. These differences in PP and particularly reduced MAP may have implications for optimal BP management in people with multimorbidity.
PS-P05-2: THE CORRELATION OF HYPERTENSION WITH LENGTH OF STAY OF ADHF IN CVCU OF SAIFUL ANWAR GENERAL HOSPITAL, MALANG, INDONESIA
Authors: Sakti Pradhika Perdana , Anjarwani Setyasih
Published: January 2023

Background:

Long-term hypertension eventually leads to heart failure (HF), and therefore, most patients with HF have a history of hypertension. Conversely, the absence of hypertension in midlife was associated with a lower risk of new-onset heart failure later in life. Cardiac remodeling with major pressure overload includes diastolic dysfunction and concentric left ventricular (LV) hypertrophy. If pressure overload persists, diastolic dysfunction progresses and concentrically remodeled left ventricular filling decreases, followed by heart failure with preserved ejection fraction.

Objectives:

The aim of this study was to ascertain the correlation of pre-existence hypertension with the length of stay (LOS) of acute decompensated heart failure (ADHF) patients admitted in CVCU of Dr. Saiful Anwar General Hospital, Malang.

Method:

The study was a retrospective analytic in ADHF patients in CVCU of Dr. Saiful Anwar General Hospital Malang in August 2021 to April 2022. The presence of pre-existence hypertension in admission were compared with non-hypertensive group.

Result:

A total of 86 patients met study criteria in August 2021 to April 2022, respectively. The prevalence of hypertensive group ADHF patients was 61.6% (53 of 86), with comparable rates for men (74.4% [64 of 86]) and women (25.6% [22 of 86]). The LOS rate was higher in hypertensive group (11 days in average) than non-hypertensive group ADHF patients (8 days in average).

Conclusion:

The prevalence of hypertension as comorbid of heart failure patients is higher than the non-hypertensive heart failure group in CVCU of Dr. Saiful Anwar Malang in August 2021 to April 2022. Based on admission vital signs, patients with longer LOS have hypertension as pre-exsistence comorbid.
PS-P05-5: CHANGES IN BLOOD PRESSURE CONTROL, TARGET ORGAN DAMAGE AND CARDIOVASCULAR RISK FACTORS IN HYPERTENSIVE SUBJECTS UNDER ANTIHYPERTENSIVES DURING 9 YEARS
Authors: Hayashi Kazusa , Takase Hiroyuki , Kin Fumihiko , Nakano Suguru , Machii Masashi , Takayama Shin , Sugiura Tomonori , Dohi Yasuaki
Published: January 2023

Objective:

Since an increase in blood pressure is one of the most important risk factors for cardiovascular morbidity and mortality, appropriate blood pressure control is necessary to prevent target organ damages and cardiovascular diseases. We investigated changes in blood pressure control, target organ damage and cardiovascular risk factors of hypertensive subjects under antihypertensive medications from 2010 to 2019.

Design and Methods:

A total of 1679 and 1884 hypertensive subjects under antihypertensive medications (62.8 ± 9.8 and 65.8 ± 9.4 year-old, respectively) who visited our hospital for physical checkup in 2010 and 1019, respectively, were enrolled. Subjects were divided into two groups; controlled (blood pressure < 140/90mmHg) and not-controlled groups (blood pressure > = 140/90mmHg). Target organ damage defined as left ventricular hypertrophy (LVH) on electrocardiogram (Sokolow-Lyon voltage > 3.8 mV and/or Cornell product > 2440 mm ms) or decline of estimated glomerular filtration rate (eGFR; < 60 mL/min per 1.73 m2) and other cardiovascular risk factors were investigated.

Results:

The results are summarized in the table. Blood pressure control was generally improved during the 9 years though the mean age of subjects was increased. The prevalence of impaired kidney function but not LVH and the number of subjects with risk factors were increased during the period. Sub-analysis in 537 subjects who visited in both 2010 and 2019 were performed and similar results were obtained (data not shown).

Conclusions:

Although blood pressure control was improved, total management of hypertensive subjects was not appropriate. Management of risk factors other than hypertension as well as blood pressure control is necessary in hypertensive subjects for extension of healthy life expectancy.
PS-P05-8: CARDIOVASCULAR DISEASES AWARENESS AMONG WOMEN IN NORTHERN JORDAN
Authors: Okour AbdelHakeem , Saadeh Rami
Published: January 2023

Background:

Womens awareness of chronic diseases, including cardiovascular diseases, is the cornerstone in promoting womens health.

Objectives:

To examine the relationship of awareness levels about cardiovascular diseases and their related risk factors with demographic information of Jordanian women.

Methods:

A cross-sectional study of 18 years and older women. Scores of awareness were computed for each individual and were divided into 4 quartiles. Logistic regression analysis was used to examine the association of demographic information of participants with mean scores of quartiles. ANOVA analysis was used to com-pare between the mean scores of quartiles.

Results:

A total of 514 women completed the questionnaire, with a mean age of 35.46 (±12.53). Current smokers were 6.2%, and 34.6% had a family history of heart disease. The proportion of diabetes, hypertension, hypercholesterolemia, and overweight/obesity were 15.6%, 19.3%, 14.4%, & 21.6% respectively. The mean score for awareness was 12.87 (+ 3.26). Women who had lower income and who were at younger age were more likely to score low in awareness.

Conclusion:

Women illustrated a fair level of awareness of CVD and its related risk factors. Increasing women awareness of CVD through educational programs, targeted toward women at risk, assists in disease prevention and help to improve treatment plans.
PS-P06-3: TREATMENT SEEKING BEHAVIOUR AND TRIGGERS AMONG PATIENTS WITH CHRONIC ILLNESSES DURING COVID-19 PANDEMIC: A QUALITATIVE STUDY
Authors: Gamage Anuji , Gunasekera Therani , Sathasivam Sridharan
Published: January 2023

Background:

Public health strategies, many of which required restricting movement of people, such as lock-downs and social-distancing measures had to be resorted to world-wide, to reduce the incidence and transmission of COVID-19, leading to a decline in healthcare utilization by non-COVI-19 patients, which is detrimental to people suffering from chronic-illnesses. This study aimed to assess treatment-seeking behavior among patients with chronic illnesses during the pandemic and the new normal.

Methods:

This qualitative study involved in-depth interviews with sixteen patients aged 30 -55 years with chronic diseases. Three focus group sessions were also held. The indepth interviews and focus group discussions were conducted until saturation point was achieved. Purposive sampling was used, and data were analyzed thematically. The study centers were two public hospitals and one general practitioner setting in Sri Lanka.

Findings:

Three main themes were identified. Namely, change of treatment seeking behaviour, difficulties in healthcare access and adherence and high out of pocket expenditure. Majority had diabetes, hypertension or both. Trigger factors for changing the healthcare setting during the pandemic were long waiting times, lack of staff to conduct the clinic, lack of drugs and investigations, and fear and anxiety associated with the pandemic. Treatment access and adherence were found difficult due to lack of high expenditure on transportation, prolonged waiting times, difficulties in buying the drugs, and spending on laboratory investigations. The reasons for high cut-off pocket expenditures were mostly for transportation, drugs, consultations and investigation. Some mentioned that due to difficulties in obtaining the treatment, they resort to adopting a healthy lifestyle, taking indigenous medication, and taking the drugs in a different frequency and regime. Very few agreed that they received the drugs via the postal service but stated that this was not regular, and that not all the drugs were available.

Conclusion:

Healthcare system-related and patient-related factors lead people to change their treatment-seeking behavior. Any health intervention to promote people's treatment-seeking behavior and to continue acess and adherence, especially for a chronic illness, should consider these complex trigger factors of individual needs, goals, and issues.
PS-P06-9: PREVALENCE OF DEPRESSIVE SYMPTOMS AMONG ADOLESCENTS WITH RHEUMATIC FEVER OR RHEUMATIC HEART DISEASE ON ANTIBIOTIC PROPHYLAXIS IN A TERTIARY HOSPITAL
Authors: Yeo Al Raymond Chiong Ramos , Mangubat Michelle Noblejas
Published: January 2023

Objective:

To determine the prevalence of depressive symptoms among adolescents diagnosed with Rheumatic Fever or Rheumatic Heart Disease on antibiotic prophylaxis at the National Childrens Hospital

Design:

A descriptive cross-sectional design that looked at the prevalence of depressive symptoms among the participants was utilized among 34 adolescents who met the inclusion criteria for the study.

Method:

This study utilized a descriptive cross-sectional design that looked at the prevalence of depressive symptoms among the adolescents ages 13–17 years old diagnosed with Rheumatic Fever or Rheumatic Heart Disease on antibiotic prophylaxis and registered at the National Childrens Hospital Cardiology Outpatient Clinic from December 1 to 31, 2021. Age, sex, duration of treatment, missed doses and presence of absence of cardiac involvement were obtained.

Results:

Thirty-four were included in this study. Majority of them were female (64.7%) with a mean age of 15.1 (SD +/-1.54). There were 29 (85.3%) who received secondary prophylaxis for more than six months at the time of interview. 28 (82.4%) were diagnosed as having Rheumatic Heart. Thirteen (38.2%) have had missed dose/s since start the of their prophylaxis. Among the 34 adolescents, 27 (79.4%) had depressive symptoms on screening with majority identified as having mild and minimal symptoms. All adolescents were followed up and advised accordingly based on the recommendations per screening results.

Conclusion:

Depression and other mental health concerns are common among adolescents, especially those with chronic health conditions such as rheumatic fever and rheumatic heart disease. Screening and initial evaluation for depressive symptoms should be done in order to identify those at risk. Prompt referrals to specialists should be facilitated when needed to prevent the unwanted consequences of depression and to improve treatment outcomes.
PS-P06-13: THE IMPACT OF BODY COMPOSITION AND ADIPOSE DISTRIBUTION ON BLOOD PRESSURE IN YOUNG AND MIDDLE-AGED ADULTS
Authors: Yu Shikai , Zhao Song , Zhang Yi , Xu Yawei
Published: January 2023

Background and Aims:

Both body size and composition are related to BP elevation. Body adipose mass and lean/muscle mass are closely related, and thus the mutual adjustment is important when investigating the impact of one of them on BP. Besides, the proportionate contributions of various components of body composition on BP remains unknown. Thus, in the present study, by constructing models including body fat mass in various depots and body muscle mass simultaneously, we aimed to comprehensively investigate the impact of body composition and adiposity distribution on BP in young and middle-aged adults.

Methods:

14412 participants with available data on whole-body DXA measurement derived from the National Health and Nutrition Examination Survey were included. Multiple stepwise linear regression models of BP on various components of body composition were built to evaluate the true determinants of BP in terms of body composition. Then, relative importance analysis was performed to quantify the contributions of various components of body composition and adipose distribution.

Results:

The mean age of the participants was 36 years and there were 50.7% women. Linear regression with mutual adjustment showed that total fat mass, total muscle mass, and trunk fat mass were significantly and positively associated with BP, respectively; however, arm and leg fat mass were significantly and negatively associated with BP. After adjusted for potential covariates, SBP were significantly determined by trunk fat mass (β; = 0.33, P < 0.001), leg fat mass (β; = -0.12, P < 0.001), and total muscle mass (β; = 0.10, P < 0.001); DBP were significantly determined by trunk fat mass (β; = 0.52, P < 0.001), leg fat mass (β; = -0.15, P < 0.001), arm fat mass (β; = -0.23, P < 0.001), and total muscle mass (β; = 0.06, P < 0.001) in men. Similar results were observed in women. Relative importance analysis indicated that trunk fat mass was the major contribution to SBP and DBP in both men and women; meanwhile, total muscle mass also made relatively great contribution to SBP for men and women.

Conclusions:

Both fat mass and muscle mass were independently associated with and substantially contributed to SBP in both men and women. After adjustment for other measurements of body composition and potential covariates, trunk fat mass was positively associated with BP and was the most dominant contributor to BP; however, leg fat mass was negatively associated with BP.
PS-R01-1: BLOOD PRESSURE FLUCTUATIONS AND THE INDOOR ENVIRONMENT WITH A HIGHLY INSULATED AND AIRTIGHT MODEL HOUSE DURING THE COLD WINTER SEASON
Authors: Nakagami Hironori , Katsuya Tomohiro , Rakugi Hiromi
Published: January 2023

At cold temperatures, blood vessels constrict to suppress heat dissipation to maintain a constant core body temperature, leading to increased blood pressure (BP). Increased BP affects the increased mortality from cardiovascular disease in cold seasons. We examined the effect of the indoor environment on BP fluctuations with an automatic BP monitor during the cold winter season (Mar 3rd to 10th in 2019), both at home and in a highly insulated and airtight model house (Model House). The indoor environments were recorded by installing data loggers equipped with temperature sensors in various rooms. BP was measured once per hour in the daytime (from 3 or 4 pm to 12 pm and from 6 am to 1 pm) and once every two hours in the nighttime (from 12 pm to 6 am). This study protocol was approved by the Nara Hospital, Kindai University Ethics Committee (No. 527). Four subjects (two couples) (Subject 1–4: 60, 59, 59, 56 years old, respectively) were enrolled, who took no medication for high BP. The room temperature at the home of Subjects 1 and 2 was low. In contrast, the room temperature of the Model House was high and stable throughout the day, even if the outside temperature at nighttime was very low on that day. The 24-hour BP of Subject 1 tended to be higher in their home than in the Model House [average ± SD (standard deviation) of the systolic BP (mmHg):131 ± 21.7 vs. 120 ± 16.6, diastolic BP (mmHg): 87 ± 14.6 vs. 82 ± 16.4]. Surprisingly, the 24-hour BP of Subject 2 was high throughout the day and was extremely higher in their home than in the Model House [systolic BP (mmHg): 171 ± 33.8 vs. 148 ± 22.7, diastolic BP (mmHg): 102 ± 20.4 vs. 88 ± 11.4]. The same trend was observed for Subject 2 in the blood pressure variation (CV) which was defined as SD divided mean BP [CV of the systolic BP (%):19.4 vs. 15.3, diastolic BP (%): 20.0 vs. 13.0]. Compared with that of Subjects 1 and 2, the room temperature at the home of Subjects 3 and 4 was relatively high in the living room, and the BPs of Subjects 3 and 4 tended to be similar in both their home and the Model House. To prevent cardiovascular events at home, a suitable indoor thermal environment for BP management should be proposed, especially in the winter season.
PS-BPB01-1: SPARC IS INDUCED AT THE EARLY STAGE OF VASCULAR ENDOTHELIAL DYSFUNCTION TO COMPENSATE INFLAMMATION IN DOCA-SALT HYPERTENSIVE RATS
Authors: Toba Hiroe , Kobara Miyuki , Nakata Tetsuo
Published: January 2023

Objective:

Extracellular matrix (ECM) regulates various cellular functions as well as provides structural support. SPARC (secreted protein acidic and rich in cysteine) is one of the ECM components, which participates in various cellular functions, especially during morphogenesis and tissue remodeling. We have reported that 1) SPARC, which increases in accordance with renal injury, causes collagen deposition through ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin type 1 motif) production, and 2) renin-angiotensin system is placed in the upstream of SPARC overexpression in the hypertensive rat kidney. The present study investigated the roles for SPARC in vascular endothelial cell dysfunction and inflammation in the setting of hypertension.

Design and method:

Rats were treated with deoxycorticosterone acetate (DOCA) and 1% salt water for 0, 1, 2 or 3 weeks. Blood pressure was measured by tail-cuff methods, and thoracic aorta was isolated to examine acetylcholine-induced vasodilatory response, macrophage infiltration by immunohistochemistry, and protein expression of SPARC and ADAMTS1 by Western blotting. In the separate experiment, angiotensin II (10–7mol/L, 6hr) or SPARC recombinant protein (100nmol/L, 24hr) was treated to cultured rat aortic endothelial cells (RAECs) with/without siRNA targeting SPARC and ADAMTS1. MCP-1 and LOX-1 mRNA levels were measured by real-time RT-PCR.

Result:

DOCA-salt caused time-dependent increases in systolic blood pressure, impairment of endothelium-dependent vasodilation, and macrophage infiltration into the adventitial area of the aorta. The expression of SPARC in the DOCA-salt rat aorta was enhanced at week1 and week2 compared to week0. ADAMTS1 expression tended to increase from week1 and showed significant increases at week3. In RAECs, SPARC and ADAMTS1 gene knockdown aggravated angiotensin II-induced overexpression of LOX-1 and MCP-1 mRNA, indicating anti-inflammatory effects of SPARC. On the other hand, SPARC recombinant protein treatment induced the upregulation of LOX-1 and MCP-1.

Conclusions:

SPARC may be induced at the early stage of vascular injury to compensate inflammation under the existence of angiotensin II. We need further investigation into the diverse effects of SPARC and the relationship between SPARC and ADAMTS1.
PS-BPB02-1: POSSIBLE DIFFERENTIAL EFFECTS OF SACUBITRIL/VALSARTAN AND VALSARTAN AGAINST HYPERTENSION AND CARDIORENAL INJURY IN A MOUSE MODEL OF CARDIORENAL SYNDROME
Authors: Tsukamoto Shunichiro , Wakui Hiromichi , Uehara Tatsuki , Azushima Kengo , Shiba Yuka , Tamura Kouichi
Published: January 2023

Objective:

Angiotensin receptor-neprilysin inhibitors (ARNI) are potential therapeutic candidates for the treatment of cardiorenal syndrome. Although evidence is accumulating on the therapeutic effects of ARNI for heart failure and hypertension, the effects of ARNI on kidney disease or cardiorenal syndrome are controversial. To address this issue, we investigated the organ-protective effect of ARNI on cardiorenal syndrome using the ANS [Ang II (A) + nephrectomy (N) + saline (S)] mice, which is the cardiorenal syndrome model.

Design and method:

C57BL/6 mice were divided into 5 groups: Control (sham operation) group, ANS (ANS + vehicle treatment) group, Val M [ANS + moderate dose of valsartan treatment (30 mg/kg/day)] group, ARNI [ANS + sacubitril/valsartan treatment (60 mg/kg/day)] group, and Val H [ANS + high dose of valsartan treatment (60 mg/kg/day)] group. Sacrifice was performed after 4 weeks, and various analyses were conducted.

Results:

ARNI, Val M, and Val H treatment groups attenuated the elevation of blood pressure in ANS mice; valsartan exerted its antihypertensive effect in a dose-dependent manner, and the antihypertensive effect of the ARNI group was intermediate between Val M and Val H groups. Regardless of the strength of the antihypertensive effect, the ARNI group was most effective in preventing the decrease in cardiac contraction and cardiac fibrosis in ANS mice. However, the ARNI group was insufficient to suppress urinary albumin excretion and renal fibrosis in ANS mice. Both valsartan groups suppressed urinary albumin excretion in ANS mice, as well as renal fibrosis and glomerular swelling. In addition, RNA sequencing analysis suggested that ARNI and valsartan may involve different molecular mechanisms in the kidney.

Conclusions:

The ARNI group showed better cardioprotective effects than both of valsartan treatment groups, but not sufficient kidney protection. These results of present study using a mouse model of cardiorenal syndrome suggested that the relationship between the antihypertensive effects and the organ protective effects of cardiorenal injury may be different between angiotensin II receptor blocker (ARB) and ARNI.
PS-BPB02-3: TARGETING FORMYL PEPTIDE RECEPTORS AS A NOVEL APPROACH TO TREAT HYPERTENSION-INDUCED ADVERSE CARDIOVASCULAR REMODELLING AND DYSFUNCTION
Authors: Singh Jaideep , Jackson Kristy L , Gumanti Audrey , Fang Haoyun , Woodman Owen L , Ritchie Rebecca H , Greening David , Head Geoffrey A , Qin Chengxue
Published: January 2023

Introduction:

Chronic unresolved inflammation has been shown to contribute to the development and progression of hypertension-induced cardiovascular damage. Failure to resolve inflammation exacerbates the risk and severity of cardiovascular disease. Currently, available therapies have limited efficacy in treating hypertension and its associated complications. Formyl peptide receptors (FPR) play a critical role in the regulation of resolution of inflammation. We have previously discovered that a FPR small-molecule prototype Cmpd17b exerts cardioprotective and vasoprotective effects against acute and severe inflammatory cardiac insults, but its impact on a chronic inflammatory insult in cardiovascular diseases, such as hypertension, has not been explored.

Aim and hypothesis:

To investigate the therapeutic potential of a FPR agonist, Cmpd17b on cardiac and vascular remodelling and function, and blood pressure regulation in hypertensive mice.

Methods:

Male C57BL/6 mice (12 weeks old) were implanted with a radiotelemetry probe to measure MAP (mean arterial pressure). Hypertensive mice (AngII infused at 0.7 mg/kg/day, subcutaneously) and normotensive mice (saline infused, subcutaneously) underwent 24-hour blood pressure recordings via telemetry at baseline and during 4 weeks daily treatment with Cmpd17b (50 mg/kg/day, intraperioneally) or its vehicle. Sympathetic nervous system (SNS) activity was assessed using power spectral analysis. At week 4, cardiac and vascular function was assessed using B-mode and M-mode echocardiography. At the end of the study, heart and arteries were collected, cardiac and vascular remodelling (fibrosis and hypertrophy) and function, and cutting-edge comparative qualitative proteomics were assessed.

Results:

Cmpd17b reduced MAP, SNS activity, cardiac and vascular adverse remodelling and dysfunction in hypertensive mice (Table). Cutting-edge quantitative proteomics analysis revealed that hypertension-induced significant adverse structural remodelling (110 proteins in the heart and 60 proteins in the aorta) and mitochondrial dysregulation (38 in the heart and 91 in the aorta), consisted with function and pathology observed. Those changes were prevented by FPR agonism (53 structural cardiac proteins and 38 vascular structural proteins) and (24 cardiac mitochondrial proteins and 36 vascular mitochondrial proteins).

Conclusions:

Our study demonstrated for the first time that FPR prototype small-molecule Cmpd17b reduced hypertension-induced cardiovascular damage, supporting the development of FPR-based therapy to treat cardiovascular complications in systemic hypertension.
PS-BPB02-4: LEFT VENTRICLE HYPERTROPHY AND DYSFUNCTION WERE EXAGGERATED BY P2RX7 KNOCKOUT BUT UNAFFECTED BY P2RX7 PHARMACOLOGIC BLOCKADE IN ANGIOTENSIN II-INFUSED MICE
Authors: Berillo Olga , Shokoples Brandon , Comeau Kevin , Higaki Akinori , Caillon Antoine , Paradis Pierre , Schiffrin Ernesto L
Published: January 2023

Objective:

Extracellular adenosine triphosphate released from damaged cells binds to the P2X7 receptor (P2RX7) to activate of immune cells. Our preliminary data demonstrated that P2RX7 plays a role in vascular injury of hypertensive mice. Angiotensin (Ang) II-induced hypertension, vascular injury and aortic perivascular infiltration of activated T cell were attenuated by P2rx7 knockout or P2RX7 pharmacologic blockade. However, whether P2RX7 is involved in Ang II-induced cardiac dysfunction and hypertrophy is unknown. We hypothesized that Ang II-induced left ventricular (LV) dysfunction and hypertrophy would be blunted by P2rx7 knockout or P2RX7 antagonism.

Design and method:

Ten-to-12-week-old male C57BL/6J wild-type (WT) and P2rx7-/-
mice were infused or not with Ang II (1000 ng/kg/min) for 14 days. A second set of Ang II-infused WT mice was infused with the P2RX7 antagonist AZ10606120 (694 ng/kg/min) or vehicle for 14 days. Cardiac LV function and remodeling were determined by ultrasound. Total RNA was isolated from the heart using the mirVana miRNA isolation kit. Relative expression was calculated using the Pfaffl method with 40S ribosomal protein S16 (Rps16) as a reference gene. Hypertrophic and fibrotic markers were studied by reverse transcription-quantitative PCR (RT-qPCR) in cardiac ventricles.

Results:

Ang II-induced 1.5-fold increase in LV mass/body weight (P < 0.001) and ∽25% decrease in fractional shortening in WT mice and mice receiving AZ10606120 (P < 0.05). These changes were exaggerated in P2rx7-/-
mice (LV mass/body weight: 1.7-fold increase, fractional shortening: 54% decrease, P < 0.05), but not in mice receiving AZ10606120. Ang II-induced atrial natriuretic peptide (Nppa/Rps16: 7-fold, P < 0.001) and α-skeletal actin 1 expression (Acta1/Rps16: 6-fold, P < 0.001) tended to be further increased in P2rx7-/-
mice (Nppa/Rps16: 14-fold and Acta1/Rps16: 12-fold), but not in AZ10606120-treated mice. Ang II-induced myosin heavy chain 7B (14-fold, P < 0.05) was unaffected by P2rx7 knockout or P2RX7 antagonism. Ang II caused a 1.5-fold increase in transforming growth factor β; 1 only in P2rx7-/-
mice (P < 0.05).

Conclusion:

Ang II-induced LV hypertrophy and dysfunction were exaggerated by P2rx7 knockout but were not affected by P2RX7 pharmacologic blockade.
PS-BPB02-8: CURCUMIN, AN INHIBITOR OF P300-HAT ACTIVITY, PREVENTS HYPERTENSION-INDUCED CARDIAC HYPERTROPHY WITH PRESERVED SYSTOLIC FUNCTION IN DAHL RATS
Authors: Sunagawa Yoichi , Hamabe-Horiike Toshihide , Funamoto Masafumi , Katanasaka Yasufumi , Hasegawa Koji , Morimoto Tatsuya
Published: January 2023

Background:

Hypertension causes left ventricular hypertrophy (LVH) with a preserved systolic function. While LVH might be a compensatory process, its presence of LVH is associated with an increased incidence of cardiovascular events and heart failure. Recently, we found that curcumin, a major curcuminoid isolated from Curcuma longa, inhibits the histone acetyltransferase (HAT) activity of p300 as well as the p300-induced acetylation of histones and a hypertrophy-responsive transcription factor, GATA-4, in cultured cardiomyocytes. Furthermore, curcumin prevents deterioration of the systolic function in rat heart failure models in vivo. However, whether curcumin prevents the development of hypertension-induced LVH at an early stage of hypertension is unclear.

Objective:

To solve this problem, we have utilized a salt-sensitive Dahl rat (DS) model of hypertension.

Methods:

We randomized 6-week-old DS (n = 19) and control salt-resistant Dahl rats (DR, n = 10) to curcumin or the vehicle group. Then, these rats were given a high-salt diet and subjected to daily oral treatment with 50 mg/kg/day of curcumin or its vehicle (1% Gum arabic) for 6 weeks.

Results:

There were no differences between curcumin and vehicle in any data examined before treatment (6 weeks of age). The high-salt diet-induced a similar degree of hypertension in these two groups of DS compared with DR. At 12 weeks of age, transthoracic echocardiography in the vehicle group showed that the LV wall thickness, LV mass, and LV fractional shortening were significantly higher in DS compared with DR, and the LV systolic and diastolic dimensions were significantly smaller in DS than DR. Curcumin treatment significantly (p < 0.01) decreased the LV wall thickness in DS but not DR. Curcumin also significantly (p < 0.01) decreased the LV mass in DS, but not in DR. However, LV fractional shortening in DS was similar between the two groups. Curcumin also prevented the increases in hypertension-induced myocardial cell hypertrophy and perivascular fibrosis. Furthermore, curcumin significantly attenuated the up-regulation of hypertrophy-response gene transcriptions as well as acetylation of GATA4 but not phosphorylation of ERK1/2 and GATA4 in the heart.

Conclusions:

The natural compound, curcumin, inhibits the development of hypertension-induced concentric LVH without affecting the systolic function through inhibition of GATA4-acetylation. Thus, this compound might be applicable to patients with early-stages hypertensive heart diseases.
PS-BPB03-3: MODIFIED ANGIOTENSIN II PEPTIDE VACCINE FOR HYPERTENSION
Authors: Baba Satoshi , Nakagami Hironori , Rakugi Hiromi
Published: January 2023

We and others recently reported that an angiotensin II vaccine for hypertension successfully attenuated elevated blood pressures in an animal model without any immunogenic side effects. In this system, an immunogenic molecule (i.e., KLH) with adjuvants provides an antigen that supports the activation of helper T cells. We recently developed a novel peptide, AJP001, that possesses both a mouse T-cell epitope and adjuvant action. Direct conjugation to the antigen is useful for peptide vaccines without the addition of adjuvants. In this study, the efficacy of an angiotensin II and AJP001-conjugated peptide vaccine (AJP001- angiotensin II) was evaluated in mice. The anti-angiotensin II antibody titer was measured in Balb/C mice following three injections of AJP001-angiotensin II at 2-week intervals. SBP was measured during vaccination of Balb/C mice treated with angiotensin II infusion. AJ-angiotensin II treatment resulted in an increase in the anti-angiotensin II antibody titer in a dose-dependent manner without the addition of adjuvants. In the analysis of the humoral immune response, AJP001-angiotensin II mainly elicited IL-4 and IL-10 production, as measured by an enzyme-linked immune absorbent spot assay, which suggests the induction of a Th2 response. Importantly, cotreatment with purified antibodies attenuated angiotensin II-induced extracellular signal-regulated kinase phosphorylation in cultured vascular smooth muscle cells. The SBP in immunized mice was significantly lower than that in nonimmunized mice (135.9 ± 8.5 vs. 154.9 ± 16.8 mmHg, P = 0.02). Furthermore, angiotensin II-induced perivascular fibrosis in the heart was significantly attenuated in immunized mice, which also exhibited decreased mRNA expression of collagen I/III and transforming growth factor-beta. It may be a simple and useful therapeutic peptide vaccine, and we now further modify the T cell epitope for clinical trials.
PS-BPB04-3: ENHANCEMENT EFFECTS OF GINSENOSIDE-RG2 ON SOME ANTIHYPERTENSIVE AGENTS-INDUCED SUPPRESSION OF ADRENAL CATECHOLAMINE RELEASE
Authors: Ki Young Jae , Koh Young Youp , Lim Dong Yoon
Published: January 2023

Objective:

The present study was aimed to investigate the effects of ginsenoside-Rg2 (Rg2), one of panaxadiol-type saponins, which is isolated from Korean Red ginseng, in some antihypertensive agents-induced reduction on the release of catecholamines (CA) from the perfused model of the rat adrenal medullae.

Design and Methods:

The adrenal gland was isolated and perfused with Krebs-bicarbonate. The CA amoiunt in the perfusate was measured directly by using the fluorospectrophotometer.

Results:

Ginsenoside-Rg2 (3∼30 μM) during perfusion into an adrenal vein for 90 min significantly inhibited the CA secretion evoked by acetylcholine (ACh) in a dose- and time-dependent fashion. Also, olmesartan (AT1 receptor blocker, 15 μM), simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, 60 μM), enalapril (an inhibitor of angiotensin converting enzyme, 150 μM), and cilnidipine (a voltage-dependent L-type Ca2+ channel blocker, 3 μM) significantly reduced the CA secretion evoked by ACh and angiotensin II (Ang II), respectively. In the simultaneous presence of ginsenoside-Rg2 (10 μM) along with four antihypertensive agents (olmesartan, enalapril, simvastatin or cilnidipine), the CA secretion evoked by ACh and Ang II was more strongly inhibited compared with that of each antihypertensive agent-treatment alone.

Conclusion:

Collectively, these results demonstrate that ginsenoside-Rg2 as well as antihypertensive agents can inhibit the CA secretion evoked by activation of both cholinergic and AT1 receptors from the perfused rat adrenal medulla. When this ginsenoside-Rg2 was used in combination with different antihypertensive agents, their effects of antihypertensive agents on reduction of adrenal CA secretion were significantly enhanced, which may also be clinically beneficial for the treatment of cardiovascular diseases.
PS-BPB05-1: DUAL DISRUPTION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE AND APOE GENE ACCELERATES KIDNEY FIBROSIS AND AGING AFTER INJURY
Authors: Kishi Seiji , Nishimura Kenji , Kashihara Naoki
Published: January 2023

Objective:

Advances in medical science have made it possible to control diseases such as cancer, autoimmune diseases, and infectious diseases, extending the lifespan of affected people around the world. On the other hand, the number of patients with Chronic Kidney Disease (CKD) is increasing worldwide, and hypertension is a key factor. Suppression of CKD is important for extending healthy life expectancy. In this study, we will clarify the effects of the interaction between hypertension and atherosclerosis on renal fibrosis and aging.

Design and method:

Wild type (WT) mouse, apolipoprotein E-/- (ApoE KO) mouse, and endothelial nitric oxide synthase (eNOS)-/- ; ApoE-/- (DKO) mouse were obtained by crossing eNOS+/- mouse and ApoE+/- mouse. Unilateral ureteral obstruction (UUO) was performed on 8–10 weeks old male mice after blood pressure and lipid profile were measured. Mice were sacrificed 10 days after UUO. The degree of renal tubular injury, fibrosis and kidney senescence were evaluated.

Results:

DKO mice exhibited the most pronounced blood pressure and lipid abnormalities among the three groups, with a significant elevation of blood pressure, total cholesterol, and low HDL cholesterol compared to WT mice. DKO mice manifested elevated blood pressure, higher total cholesterol and lower HDL than WT mice. Compared with WT mice, ApoE KO and DKO mice showed sustained kidney injury molecule-1 expression and kidney fibrosis was significantly higher in ApoEKO and DKO mice. mRNA expression of genes related to kidney fibrosis was the highest in DKO mice. The mRNA expression of Zinc alpha2 Glycoprotein and heme oxygenase-1 were significantly decreased in DKO mice. Furthermore, mRNA expression of p53, p21 and p16 were increased both in ApoEKO and DKO mice, with DKO mice being the highest. Senescence associated beta-gal positive tubule area was significantly increased in DKO. Increased DNA damage and target of rapamycin autophagy spatial coupling compartments (TASCCs, Sci Transl Med. 2019;11(476):eaav4754. J Clin Invest. 2019;129(11):4797- 4816.) formation was found in DKO mice.

Conclusion:

Mice at high risk for cardiovascular disease developed kidney fibrosis and aging even in the young mice after injury. Vulnerability to oxidative stress due to endothelial cell dysfunction promotes fibrosis and aging. Managing lifestyle-related diseases including hypertension from a young age is important for CKD prevention.
PS-BPB05-3: SERINE PROTEASE INHIBITION EXERTS AQUARETIC EFFECT AND DECREASES URINARY EXOSOMAL AQP2 LEVELS
Authors: Kakizoe Yutaka , Iwata Yasunobu , Nakagawa Terumasa , Deng Qinyuan , Adachi Masataka , Miyasato Yoshikazu , Nakagawa Miyuki , Nagayoshi Yu , Nishiguchi Kayo , Narita Yuki , Izumi Yuichiro , Kuwabara Takashige , Mukoyama Masashi
Published: January 2023

Objective:

Serine proteases (SPs) play pivotal roles in various physiological processes. In the kidney, it is reported that the epithelial sodium channel (ENaC) is activated via the proteolytic cleavage of α and γ subunits by SPs. We previously reported that a synthetic SP inhibitor camostat mesilate (CM) suppressed the cleavage of γENaC, thereby decreasing sodium reabsorption and blood pressure in aldosterone-infused rats. These results suggest the important roles of SPs within the kidney in the regulation of sodium homeostasis and blood pressure. Here, we aimed to identify novel physiological roles of SPs in the renal tubule and understand the mechanism of actions of SP inhibitors by administering CM into healthy rats.

Design and method:

Six-week-old male Sprague-Dawley rats were divided into control and CM groups. CM group rats were subcutaneously implanted with sustained-release pellets of CM (14 mg/day). After 24 h urine collection was performed, rats were sacrificed at day 7 to obtain blood and kidney samples. Urine volume was measured during the experimental period, and blood and urinary electrolytes, blood vasopressin, and renal tissue osmolality were measured. Protein expression of SPs and aquaporin-2 (AQP2) was analyzed by Western blotting.

Results:

CM significantly increased urine volume by approximately two-fold throughout the experimental period [urine volume (mL/day): control, 15.5 ± 2.4; CM, 30.6 ± 5.8], in a urinary sodium and osmolyte excretion-independent manner, which indicated that free water excretion had occurred. The vasopressin, potassium, and calcium levels in the blood and osmolality in the inner medulla, which affect free water reabsorption in the renal tubule, remained unchanged after CM administration. CM decreased urinary exosomal AQP2 excretion, suggesting that the AQP2 activity was suppressed in the collecting duct. These changes were reversed by the infusion of desmopressin. Such water diuretic action caused by CM was independent of its action on prostasin and TMPRSS4, which are serine proteases associated with sodium and water homeostasis, respectively.

Conclusion:

Our results revealed the association of SP inhibition with free water diuresis in the kidney and demonstrated that CM administration resulted in the downregulation of AQP2. The current findings suggest that SP inhibitors could become a new class of aquaretic drugs.
PS-BPB05-7: UPREGULATION OF ALDOSTERONE SYNTHASE INDUCED BY LUTEINIZING HORMONE IN HUMAN ADRENOCORTICAL CELLS
Authors: Morishima Noriko , Morimoto Satoshi , Watanabe Daisuke , Kato Yoichiro , Shibata Noriyuki , Ichihara Atsuhiro
Published: January 2023

Objective:

Plasma aldosterone concentration (PAC) is increased in stages of elevation of luteinizing hormone (LH) during the luteal phase of the ovarian cycle, menopause, or pregnancy. PAC is elevated in patients with polycystic ovary syndrome who have elevated circulating concentration of luteinizing hormone (LH). In addition, stimulation of aldosterone production by LH has been reported. In the present study, we investigated the mechanism by which LH increases aldosterone production in human adrenocortical cells.

Design and Methods:

Immunohistochemical staining for CYP11B2, the aldosterone synthase, and LH receptor were performed using autopsy adrenal gland specimens. Changes in mRNA or protein expressions of CYP11B2 after treatment with LH, angiotensin (Ang) II, or LH+Ang were compared in human HAC15 adrenocortical cells. Effects of an Ang receptor blocker (ARB), adenylyl cyclase (AC) inhibitor, cyclic AMP response element binding protein (CREB) inhibitor, protein kinase A (PKA) inhibitor, or β;-catenin inhibitor on the increase in CYP11B2 mRNA expression induced by LH+Ang ll were investigated in these cells. In addition, effects of an AC agonist on CYP11B2 mRNA expression were investigated in these cells.

Results:

Immunostaining for LH receptor was detected in cells positive for CYP11B2 in adrenal granulosa and fasciculata region in the human autopsy specimens. CYP11B2 mRNA and protein expressions were significantly increased after treatment with LH+Ang ll than LH or Ang ll alone in HAC cells. Elevation of CYP11B2 mRNA expression induced by LH+Ang ll was completely suppressed by the ARB, AC inhibitor, or CREB inhibitor and was significantly reduced by the PKA inhibitor or β;-catenin inhibitor in these cells. CYP11B2 mRNA expression was significantly increased by the AC agonist.

Conclusion:

The present study showed that LH receptor is expressed in human adrenal cortical region and that LH augments CYP11B2 expression via AC-CREB pathway in the presence of Ang ll in human adrenocortical cells.