bluuebunny/crossref_metadata_2025 huggingface dataset:
ENHANCING INTERACTIONS BETWEEN MASR AND ETBR AS A NEW VASOPROTECTIVE STRATEGY
Authors: Kuriakose Jithin , Montezano Augusto C , Hood Katie Y , Alves-Lopes Rheure , Sin Angie Yy , Passaglia Patricia , Finaly Jane E , Basheer Sehrish , Yusuf Hiba , Hepburn Ross , Santos Robson A , Maclean Margaret R , Baillie George S , Touyz Rhian M
Published: April 2021

Objective:

We demonstrated that the MAS and ETB receptors physically interact and may be involved in the protective actions of Ang(1–7) in endothelial cells (ECs). We assessed the biological role of MAS/ETBR interaction in the vasculature, focusing on the NO pathway.

Design and method:

Human ECs were stimulated with Ang(1–7) (10-7 M) in the presence/absence of A779 (MAS antagonist, 10-5 M), BQ788 (ETBR antagonist, 10-5 M) and MAS/ETBR peptide disruptor (10-5 M). ETBR expression and AKT/eNOS activation were evaluated by immunoblotting and NO production by DAF-FM fluorescence.

Results:

Ang(1–7) increased ETBR expression (50%), an effect blocked by A779 (p < 0.05 vs control). Ang(1–7) also induced AKT (40%) and eNOS (35%) activation; followed by an increase in NO production (2 fold) (p < 0.05 vs control). These effects were inhibited by A779, BQ788 and the MAS/ETBR disruptor. In a high throughput screening of a 20K protein:protein interaction modulator library, we discovered 23 potential enhancers of the MAS/ETBR interaction, where we tested 4 in ECs (Enh1–4: 10–5 M). All four MAS/ETBR enhancers increased eNOS activation with variable responses (Enh1: 44.2%; Enh2: 65.4%; Enh3: 80.7%; Enh4: 94.9% vs control, p < 0.05), but only treatment with Enh1 and Enh2 increased NO production (Enh1: 109.4%; Enh2: 46.5% vs control, p < 0.05) in ECs. Mesenteric resistance arteries were pre-incubated with Enh1–4 for 30 minutes prior to acetylcholine (Ach) curves, to assess endothelium-dependent relaxation. Enh1 decreased ACh-induced relaxation (Emax: 52.8 ± 2.9 vs Emax control: 70.4 ± 3.3), while Enh4 increased ACh-induced relaxation (Emax: 96.7 ± 4.6 vs Emax control: 70.4 ± 3.3), p < 0.05.

Conclusions:

Promoting the MAS/ETBR interaction with specific enhancers leads to eNOS activation and vasorelaxation, where Enh1–4 have variable effects. Current studies are focusing on identifying the most sensitive enhancer that will provide vasoprotection, and potentially new strategies in the treatment of vascular disease.
PARACHUTING - BUNGEE - MENTAL STRAIN WITH DISSIMILAR CARDIAC AND METABOLIC IMPACT
Authors: Kisters Klaus , Moser M. , Opresnik S. , Seibert F. , Porta S.
Published: April 2021

Objective:

Parachuting and bungee jumping result in heavy mental strain with dissimilar cardiac and metabolic impact. In addition changes in blood pressure values and electrolyte metabolism may occur.

Therefore it was of interest to study blood pressure and ionized magnesium values as stress markers.

Design and method:

Out of 100 microlitres of capillary blood from 23 parachuters and of 15 bungee jumpers sampled before and after the jump, blood glucose and ionized magnesium concentrations were determined by a NOVA Phox-M device, distributed by TECOM, Austria. Blood pressure values were measured by Beurer Instrumentation, Ulm, Germany.

Results:

1. Parachuting:

Sytolic and diastolic blood pressure values increased significantly after the jump (p < 0.01).

Heart rate did not change significantly.

Blood glucose and ionized magnesium values decreased significantly from initially high normal values (p < 0.01).

2. Bungee jumping:

Also no difference in heart rate, but a slight fall in systolic and a significant fall in diastolic blood pressure values after the jump were noted (p < 0.01).

Blood glucose increased from already high basal levels and ionized magnesium values decreased significantly (p < 0.01).

Conclusions:

Outright stress determines the sympathoadrenal anticipation, epinephrine challenge should be not dissimilarly high. However, a longer anxiety period during the para-jump proceedings could lead to time dependent contrary reactions in blood pressure, magnesium and glucose levels, all of them stress markers of different sensibility.

Taken together:
ANGIOTENSIN II INDUCED SALT-SENSITIVE HYPERTENSION ASSOCIATED WITH INVERSE CIRCADIAN PATTERN IN RENAL GENERATION OF TUMOR NECROSIS FACTOR ALPHA AND ANGIOTENSINOGEN IN MICE
Authors: Majid Dewan S A , Navar L. Gabriel , Castillo Alexander , Khan Nadia , Shindler Isabella
Published: April 2021

Objective:

Blood pressure (BP) in humans normally follows a circadian dipping pattern with a decline from day (active) to a night (inactive) period. Such dipping pattern is altered to a non-dipping pattern in salt-sensitive hypertension (SSH), the pathophysiological mechanism of which is not yet clearly understood. Angiotensin II (AngII) induced SSH associated with increased intrarenal AGT generation, which can be suppressed by tumor necrosis factor-alpha (TNFa) formation. We examined the hypothesis that AngII-induced TNF and AGT generation follows an inverse circadian pattern with a decrease in TNF during inactive period that facilitates increased AGT generation leads to non-dipping pattern in SSH.

Design and method:

Experiments were performed in mice (C57BL6 strain) chronically treated with or without AngII (25 ng/min; osmotic mini-pump) and high salt (HS; 4% NaCl) containing diets for 4 weeks. BP was measured at day and night periods by tail-cuff method. Circadian rhythm in urinary parameters in these nocturnal animals was assessed by 12 hour urine collections using metabolic cages during the active period (7PM to 7AM) and the inactive period (7 AM to 7 PM).

Results:

In untreated rats (n = 6), mean BP showed dipping pattern (90 ± 3 to 78 ± 2 mmHg from active to inactive period) AngII + HS treatment (n = 6) induced a non-dipping pattern of SSH (109 ± 2 to 106 ± 3 mmHg from active to inactive period). In untreated mice, urinary excretion of TNFa (uTNFa) was higher (0.5 ± 0.2 vs 0.13 ± 0.08 pg/hour) but urinary excretion of AGT (uAGT) was lower (0.28 ± 0.18 vs 0.46 ± 0.14 ng/hour) during the active period compared to that during the inactive period. This inverse relationship between uTNFa and uAGT was exaggerated in AngII+HS treated mice. There were marked increases in uTNFa during active periods (44.6 ± 14.6 pg/hour) which were less during inactive periods (12.1 ± 4.7 pg/hour). Interestingly, uAGT increment was lower during active periods (1.42 ± 0.97 ng/hour) than that in inactive periods (3.98 ± 1.67 ng/hour).

Conclusions:

TNFa generation suppresses intra-renal AGT formation during active periods but this phenomenon is inversed during inactive periods. The increase in AGT during the inactive period may facilitates a non-dipping BP pattern in SSH.
THE IMPACT OF ANTIHYPERTENSIVE DRUGS ON VASCULAR RIGIDITY AND ON THE GRADIENTS OF ARTERIAL STIFFNESS: A PILOT STUDY
Authors: Garneau Charles-Antoine , Fortier Catherine , Duval Karine , Agharazii Mohsen
Published: April 2021

Objective:

Damages to barosensitive organs would be induced by the reversal of the arterial stiffness gradient. Our team has demonstrated that administration of nitroglycerin reduces regional stiffness of muscle arteries (radial and femoral) without modifying aortic stiffness, resulting in increased aortic-brachial (AB-PWV) and aortic-femoral (AF-PWV) stiffness gradients. The aim of this project is to study the impact of antihypertensive treatment on arterial stiffness, particularly on stiffness gradients.

Design and method:

This pilot study was performed in 19 hypertensive patients (age: 71 ± 11 years, men: 85%). The aortic, brachial and femoral stiffnesses were respectively measured by the carotid-femoral (cf-PWV), carotid-radial (cr-PWV) and femoral-dorsalis pedis (fd-PWV) pulse wave velocity during 2 visits: with and without medication for high blood pressure. During the drug-free visit, patients were to stop taking their antihypertensive drugs 2-3 days before their assessment, depending on their condition. The AB-PWV and AF-PWV ratios were obtained by dividing cf-PWV by cr-PWV or fd-PWV respectively.

Results:

At the visit without antihypertensive drugs, the cf-PWV, cr-PWV and fd-PWV were respectively 12.91 ± 0.65 m/s, 9.6 ± 0.4 m/s and 10.3 ± 0.3 m/s, resulting in an AB- ratio PWV of 1.37 ± 0.09 and an AF-PWV ratio of 1.21 ± 0.07. At the visit with medication, a significant decrease in mean arterial pressure of 9.5 mmHg (p < 0.001) was observed. In addition, reductions in cr-PWV of 0.79 m/s (p = 0.034) and fd-PWV of 0.45 m/s (p = 0.29) were noted, with no statistically significant change in cf-PWV (p = 0.83), leading to a non-significant increase in the AB-PWV (p = 0.21) and AF-PWV (p = 0.52) ratios.

Conclusions:

The preliminary data from this pilot project, although statistically non-significant, evolves in the same direction as those obtained with the administration of nitroglycerin. Indeed, there is a decrease in brachial and femoral stiffness leading to an increase in the gradients, which could have consequences for the microcirculation. These results suggest an impact of antihypertensive drugs on peripheral arteries and the vascular stiffness gradients, which could be confirmed with the continuation of this project on a larger sample.
A NOVEL URINARY BIOMARKER PREDICTS 1 YEAR MORTALITY AFTER DISCHARGE FROM INTENSIVE CARE
Authors: Zhang Zhen-Yu , Nkuipou-Kenfack Esther , Latosinska Agnieszka , Yang Wen-Yi , Fournier Marie-Céline , Blet Alice , Mujaj Blerim , Thijs Lutgarde , Feliot Elodie , Gayat Etienne , Mischak Harald , Staessen Jan , Mebazaa Alexandre
Published: April 2021

Objective:

The urinary proteome reflects molecular drivers of disease. The aim of this study was to construct a urinary proteomic biomarker predicting 1 year post ICU mortality.

Design and method:

In 1243 patients, the urinary proteome was measured on ICU admission, using capillary electrophoresis couple with mass spectrometry along with clinical variables, circulating biomarkers (BNP, hsTnT, active ADM, and NGAL) and urinary albumin. Methods included support vector modelling to construct the classifier, Cox regression, the integrated discrimination (IDI) and net reclassification (NRI) improvement and area under the curve (AUC) to assess predictive accuracy, and Proteasix and protein-proteome interactome analyses.

Results:

In the discovery (deaths/survivors, 70/299) and test (175/699) datasets, the new classifier ACM128, mainly consisting of collagen fragments, yielding AUCs of 0.755 (95% CI, 0.708–0.798) and 0.688 (0.656–0.719), respectively. While accounting for study site, clinical risk factors, hazard ratios in 1243 patients were 2.41 (2.00–2.91) for ACM128 (+1 SD), 1.24 (1.16–1.32) for the Charlson Comorbidity Index (+1 point), and > = 1.19 (P < = 0.022) for other biomarkers (+1 SD). ACM128 improved (P < = 0.0001) IDI (>= + 0.50), NRI (>= + 53.7) and AUC (>= + 0.037) over and beyond clinical risk indicators and other biomarkers. Interactome mapping, using parental proteins derived from sequenced peptides included in ACM128 and in-silico predicted proteases, including/excluding urinary collagen fragments (63/35 peptides), revealed as top molecular pathways protein digestion and absorption, lysosomal activity and apoptosis.

Conclusions:

The urinary proteomic classifier ACM128 predicts the 1-year post ICU mortality over and beyond clinical risk factors and other biomarkers and revealed molecular pathways potentially contributing to a fatal outcome.
VON HIPPEL-LINDAU SYNDROME PRESENTING AS PHEOCHROMOCYTOMA COMPLICATED WITH MYOCARDIAL INFARCTION: A CASE REPORT
Authors: Yu Huizhen , Lin Lichao , Yu Peng , Chen Qing , Deng Chaochao
Published: April 2021

Objective:

Von Hippel-Lindau syndrome (VHL), a rarely inherited disease with autosomal-dominant transmission, can be characterized by pheochromocytoma complicated with various clinical manifestations, such as paroxysmal hypertension, myocardial infarction, arrhythmia, and heart failure. The related case reports are rare, especially referring to myocardial infarction. However, it is important to obtain such a clinical case, since it may facilitate diagnose by utilization of genetic testing and prognosis by early surgical treatment.

Design and method:

A 53-year-old male patient presented with recurrent and progressive chest pain, hypertension, sweating and palpitation, associated with significant 15-year history of hypertension. Although these symptoms persisted 8 months, he did not receive any treatment before first hospitalization. Transthoracic echocardiography revealed left ventricular enlargement, left ventricular wall thickening, and the decrease of ejection fraction. Blood tests showed significant troponin I, catecholamine, and 24 hours urinary vanilla mantellic acid. ECG showed sinus tachycardia with ischemic changes. Besides, abdominal computed tomography scan revealed a tumor of 5.3 cm in diameter in the right adrenal gland. Thus, the patient was required to remove the tumor after 6 months. However, he hospitalized again due to those deteriorating symptoms. Coronary angiography revealed the left anterior descending stenosis 70%. Then he was admitted to intensive care unit and died of cardiogenic shock.

Results:

A diagnosis of this VHL syndrome was finally confirmed by genetic pedigree of the family and genetic testing. Gene tests showed that the patient and his daughter carried VHL gene c.G250C heterozygous missense mutation (VHL: p.V84L het), but the elder son without mutation in the same site. VHL type 2C, a subtype of VHL, is characterized by presenting as pheochromocytoma complicated with myocardial damage, myocardial infarction and heart failure.

Conclusions:

Test of the VHL gene mutation is necessary for the patients presenting as pheochromocytoma with myocardial infarction and their asymptomatic family members. Moreover, early surgical excision of pheochromocytoma may improve the prognosis of this disease.
AQUAPORIN-3 AND CYBA GENETIC POLYMORPHISMS MAY PREDICT RISK OF DEVELOPING HYPERTENSION
Authors: Da Silva Ines Margarida Vieira , Santos Ana Carolina , Matos Andreia , Da Silva Alda Pereira , Areias Maria Jose , Soveral Graça , Rebelo Irene , Bicho Manuel
Published: April 2021

Objective:

Preeclampsia, a placentation disorder, affects 7% of pregnancies in Europe. It influences future cardiovascular disease, such as hypertension. Preeclampsia and hypertension have been associated with oxidative stress, therefore, key proteins in redox signaling may be involved with the development of hypertensive disorders during/after pregnancy. This study aimed at determining associations between oxidative stress-related gene polymorphisms (AQP3-rs2231231 and CYBA-rs4673) with the development of preeclampsia and the risk for future hypertension.

Design and method:

A cohort of 150pregnant Caucasian women, aged 35.24 ± 5.47 years, 60(40%) normotensive and 90(60%) preeclamptic, was evaluated. Based on a prospective study(2–16 years later), these women were evaluated for the development of hypertension and classified as normotensive 98(67%) or hypertensive 48(33%). The influence of genetic polymorphisms on the susceptibility for cardiovascular disease was evaluated. In this cohort, anthropometric/haemodynamic parameters were studied. For statistical analysis chi-square and Student t-test were used.

Results:

During pregnancy, no differences between the distribution of studied genetic polymorphisms in preeclampsia were found. However, based on the AQP3 dominant model of A, our data showed that AA+AC genotypes were more frequent (73.3%;p = 0.014) in hypertensive individuals. Moreover, allele A, the allele of risk, was associated with a 3.405-fold higher risk (p = 0.016,OR = 3.405,95%CI[1.26–9.19]) to develop hypertension after pregnancy. In addition, a higher systolic(p = 0.017) and diastolic(p = 0.008) pressure were also observed in women carrying the AA+AC genotype. Furthermore, based on CYBA dominant model of C, TT genotype of polymorphism was also correlated with the development of hypertension(100.0%;p = 0.007) after pregnancy. On the other hand, looking at the recessive model of C, CT+TT genotype was associated with the development of hypertension. Allele T, the allele of risk, was associated with 6.5-fold risk (p = 0,024,OR = 6.500,95%CI[1.28–33.03] to develop hypertension. Moreover, CT+TT genotypes of CYBA genetic polymorphism were more associated with increased weight (p = 0.014), higher waist circumference(p = 0.010), hip(p = 0.008) and systolic(p < 0.001) and diastolic blood pressure(p < 0.001).

Conclusions:

In this study, AQP3 genetic polymorphism was found associated with the hypertensive disorders after pregnancy for the first time. In addition, CYBA was also associated with the development of essential hypertension. These results open new perspectives in the development of new approaches for cardiovascular disease prevention.
A MULTI-SITE ANALYSIS OF THE HUMAN GUT MICROBIOME AND METABOLITES IN ASSOCIATION WITH AMBULATORY BLOOD PRESSURE
Authors: Marques Francine , Tsyganov Kirill , Ribeiro Rosilene , Gill Paul , Nakai Michael , Carrington Melinda , Yiallourou Stephanie , Muir Jane , Head Geoffrey A. , Kaye David
Published: April 2021

Objective:

High blood pressure (HBP) is a major risk factor for cardiovascular disease (CVD) and the prevalence of both is higher in regional versus metropolitan areas. The gut microbiome has emerged as important contributor to HBP, however, the relationship between BP and specific gut microbes and their metabolites is unclear. Here we aimed to determine if specific gut microbes and key metabolites such as short-chain fatty acids (SCFAs) were associated with 24 h BP whether geographic differences exist in Australia.

Design and method:

We recruited 70 subjects from the community in metropolitan (n = 40) and regional (n = 30) locations in Australia. White coat hypertension was present in 6% and masked hypertension in 19% of the cohort, and 34% were hypertensive. We assessed office and ambulatory BP, dietary intake via food frequency questionnaire, gut metabolites by gas-chromatography, and gut microbiome by 16S sequencing.

Results:

Mean(±SD) 24 h mean arterial pressure was 90.5 ± 10mmHg, systolic BP 122.8 ± 14.9mmHg, and diastolic 74 ± 8.4mmHg. There was a positive correlation between plasma short-chain fatty acid butyrate and 24 h systolic (r = 0.31, P = 0.01) and diastolic BP (r = 0.29, P = 0.02), confirmed by logistic regressions adjusted for age, sex and BMI (P = 0.001). Fifty seven genus were significantly correlated with diastolic BP (r = 0.38–0.41) after adjustment for multiple comparisons (FDR < 0.1). Inverse Simpson index, a marker of alpha diversity, was negatively correlated with 24 h mean arterial pressure (r = -0.24, P = 0.04), being driven particularly by 24 h diastolic BP and day BP. There were no differences in alpha or beta diversity between metropolitan and regional areas. Participants from metropolitan areas, however, had significantly lower levels of total SCFAs, acetate and butyrate (P < 0.05) without having any differences in fibre intake.

Conclusions:

This is the first study to analyse BP as a continuous variable, suggesting it is associated with a less diverse gut microbiome, higher levels of butyrate, and several genus of gut bacteria. Further studies will need to determine a causal relationship for these associations. We did not find a gut microbial difference between metropolitan and regional participants, but the latter had lower levels of SCFAs, which could help explain their predisposition to hypertension and cardiovascular disease.
COMMON VARIANTS OF THE NDUFS8 GENE DO NOT CONFER GENETIC SUSCEPTIBILITY TO HYPERTENSIVE LEFT VENTRICULAR HYPERTROPHY IN HAN CHINESE
Authors: Guo Hao , Yu Zi-Yang , Zhang Xing , Zhu Cheng-Zhen
Published: April 2021

Objective:

Left ventricular hypertrophy (LVH) is the most common target organ damage in essential hypertension. The serious degree of LVH is not proportional to the history of hypertension and level of blood pressure. It is suggested that other factors than hypertension are involved in the process of cardiac remodeling in hypertensive patients. Mitochondria dysfunction plays a vital role in the pathophysiology of hypertensive cardiac hypertrophy. The NADH dehydrogenase Fe–S protein 8 (NDUFS8) is one of the highly conserved nuclear-encoded subunits existing in human mitochondrial complex I. Defects in this subunit have been associated with Leigh syndrome, which is a diverse spectrum of clinical manifestation such as hypertrophic cardiomyopathy, psychomotor impairment, difficulty feeding and respiratory abnormalities. The study aim is to investigate whether the encoding NDUFS8 gene has associated with essential hypertension and hypertensive LVH.

Design and method:

In total of 1604 subjects, were Chinese-Han from Yunnan province, including 985 patients with essential hypertension (470 males and 515 females) and 619 healthy controls(240 males and 379 females). Six NDUFS8 tagSNPs (rs3751084, rs999571, rs2075626, rs1104739, rs3133269 and rs11228127) were genotyped and major haplotypes consisting of these six SNPs were reconstructed for all subjects.

Results:

The common genetic variants of the NDUFS8 genes have not positive associated with essential hypertension and hypertensive LVH. Haplotype GGCCTA was nominally significant associated with essential hypertension (P = 0.046). Nevertheless, no significant association was detected between the haplotype and the essential hypertension after bonferrioni corrections. Intriguingly, one NDUFS8 tagSNP (rs3751084), which showed marginally significant associated with decrease serum magnesium level, the patients’ frequency of the G allele of rs3751084 was significantly higher than among the healthy controls(P = 4.69 × 10-6).

Conclusions:

Our study indicated that common genetic variants of the NDUFS8 gene are unlikely to be involved in essential hypertension and hypertensive LVH. Of note, we can probably consider the rs3751084 as a significant regulator to serum magnesium level. Further studies are essential to characterize the role of the rs3751084-G in Torsades de points arrhythmia with hypomagnesemia.
HUMAN RENAL RNA-SEQ IDENTIFIES RELATIONSHIP BETWEEN UMOD EXPRESSION AND MEDULLARY ION TRANSPORTERS
Authors: Fisher Simon , Molina Rafael Crespo , Graham Delyth , Mcbride Martin
Published: April 2021

Objective:

Our previous genome wide association study (GWAS) highlighted a locus on the promoter of the human UMOD gene associated with hypertension. In this study, we sought to identify potential pathways which facilitate the association of UMOD with blood pressure through effects on gene expression.

Design and method:

From our bank of 98 human renal biopsy samples, we assessed UMOD and NKCC2 expression by qRT-PCR. Individuals were stratified by UMOD expression and RNA-sequencing using the NextSeq-500 system performed on a subset of high and low UMOD expression (n = 3/ group). Differential expression was assessed by DESeq2 to detect significant differences (p [adjusted] <0.05) in the transcriptome between high and low UMOD expressers and pathways visualised using Ingenuity Pathway Analysis (IPA).

Results:

RNA-Seq analysis identified 162 differentially expressed genes (138 protein coding genes,18 long non-coding RNAs and 8 additional transcriptomic elements), of these, 123 genes increased in expression with high UMOD expression. Using IPA, we detected enrichment for pathways related to immune system function, cell to cell communication and molecular ion transport. Notably, we show that an increase in UMOD expression associates with an increase in expression of the Na-K-Cl cotransporter (NKCC2) (p [adjusted] = 2.58e-9, fold-change = 10.89), the renal outer medullary potassium channel (ROMK) (p [adjusted] = 3.69e-2, fold-change = 2.79) and the gamma-subunit of the epithelial sodium channel (ENaC) (p [adjusted] = 1.83e-2, fold-change = 1.25). We further validated the relationship between UMOD and NKCC2, by Taqman qRT-PCR, showing a highly significant correlation of expression (p = 2.2e-16, R = 0.844) (n = 86). Using IPA we show this correlation may be facilitated by the transcription factor POU3F3, which can act at motifs found on promoters of both genes.

Conclusions:

Of several pathways identified by IPA, association of UMOD expression with expression of these three ion channels (NKCC2, ROMK and ENaC) may explain previously observed relationship between UMOD and blood pressure. These data suggest the UMOD: ion-transport pathway may be a drug target in the treatment of hypertension.
CORRELATION BETWEEN PEANUT SKIN PHENOLIC COMPOUNDS AND THEIR EFFECTS ON DYSLIPIDEMIA IN SWISS MICE
Authors: De Melo Kamilla Correia , Lins Lais Pinheiro , Costa Danilo José De Almeida , Rocha Aline Tavares , Neto Inácio De Barros Melo , Da Silva Joelmir L. Veiga , Pereira Schirley Almeida C. , Costa Lorena De Farias Pimentel , Gomes Felippe Barbosa , Silva Jose Sergio N. , Oliveira Thárcia Kiara Beserra De
Published: April 2021

Objective:

To characterize the secondary metabolites of aqueous peanut extract (EAAsp) plus 1% of skin (EAAcp) and its effects combined with a hyperlipidic diet in male Swiss mice, analyzing serum concentrations of biochemical analysis.

Design and method:

The pulp extract was prepared at a 1:8 ratio to obtain a final concentration of 1.25 mg/mL and added 1% peanut skin to the total volume. Polyphenols and flavonoids quantifications were used following official methodologies. The experiment was performed divided into groups (n = 10): GI - received hypercholesterolemic diet plus 0.5 mL of EAAsp daily; GII - received hypercholesterolemic diet plus 0.5 ml EAAcp. Diet time was 12 weeks. Animal weights were evaluated weekly and at the end of the experiment biochemical analyzes were performed. The difference into mean was analyzed by Tukey test, when values of p < 0.05 were considered significant.

Results:

Regarding phenolic compounds, lower values for EAAsp (3.3 mg EAG/g) were found when compared to the EAAcp formulation (5.7 mg EAG/g), demonstrating a high polyphenols potential for the skin enriched extract. For flavonoids, values of 1.78 + 0.001 for EAAsp and 4.30 + 0.001 for EAAcp were obtained with an average difference of 2.52 mg/100 g. The incorporation of peanut skin in the EAA resulted in the increasing of phenolic compounds concentration that contribute to antioxidant activity. In vivo, the extracts decreased LDL-cholesterol levels (GI-56 ± 2.2 x GII-9.8 ± 1.0), however EAAcp was more efficacy (p < 0.05) as well as the total cholesterol levels (GI-126 ± 12.7 x GII-90 ± 10.5). Both extracts decreased CRP (C-reactive protein) values in a similar manner (GI-0.96 ± 0.2 x GII-0.93 ± 0.23). Reduction in LDL-cholesterol levels could be attributed to the chemical composition of peanut skin that may promote reduced risk of cardiovascular disease.

Conclusions:

The peanut skin enriched the extract as antioxidant potential that probable greater efficacy in the reducing blood lipid levels, but it preserved the decreasing CRP levels.
SEX AND SALT-RESPONSIVE CONJUGATION OF BILE ACIDS BY THE HOLOBIONT REGULATES HYPERTENSION
Authors: Chakraborty Saroj Chakrabort , Lulla Anju , Cheng Xi , Mccarthy Cameron G , Yeo Ji-Youn , Alimadadi Ahmad , Mandal Juthika , Saha Piu , Yeoh Beng San , Louis Evangelina F , Mell Blair , Jia Wei , Wenceslau Camilla F , Vijay-Kumar Matam , Meyer Katie , Joe Bina
Published: April 2021

Objective:

Men and women are differently prone to cardiovascular diseases. Salt-sensitive women are more likely to develop aggravated hypertension in response to an overloaded salt diet than men. Men and women also differ in gut microbiota, which regulates both bile acid composition and hypertension; however, whether sex may differentially influence the gut microbial production of bile acids, with attendant effects on hypertension, is not known. We hypothesized that reshaping of gut microbiota by dietary salt is sex-dependent and adversely affects bile acids to promote hypertension.

Design and method:

To test this hypothesis, groups of male and female salt-sensitive hypertensive (Dahl S) and salt-resistant normotensive (Dahl R) rats (n = 6/gp) on low (0.3% NaCl) or high (2% NaCl) diets were profiled for fecal microbiota by 16S sequencing and serum bile acids by targeted GC-TOF-MS metabolomics.

Results:

Hierarchical clustering analysis of bile acids with microbiotal profiles revealed that glycine- and taurine-conjugated bile acids were prominently negatively correlated with blood pressure (BP) in female rats, while only taurine-conjugated bile acids were negatively correlated with BP in male rats. These observations were corroborated by microbiotal and bile acid metabolomic profiling of human hypertensive samples from a population-based cohort (CARDIA). Next, to test whether hypertension can be prevented by supplementing substrates for bile acid conjugation, high salt fed S rats were administered with either taurine (3% v/v in drinking water) or glycine (1% v/v in drinking water) in drinking water, monitored for BP by telemetry, and profiled for bile acid metabolites. Both taurine and glycine feeding prevented hypertension in females (Systolic BP: taurine:176 ± 7∗, glycine: 182 ± 4∗, control: 197 ± 4 mmHg, n = 6–9/gp, ∗p < 0.05) likely by rescuing levels of levels of respective conjugated bile acids, whereas only taurine, but not glycine, prevented hypertension in males (Systolic BP: taurine: 166 ± 2∗, glycine:184 ± 5, control: 184 ± 8 mmHg, n = 5–6/gp, ∗p < 0.05).

Conclusions:

Our results connect sex-specific differences in salt-sensitive hypertension to the gut-liver axis and suggests that nutritional restoration of host taurine- or glycine-conjugated bile acids for women and host taurine-conjugated bile acids for men as potential therapeutics for salt-sensitive hypertension.
SCREENING FOR GENETIC MUTATIONS IN LDLR GENE WITH FAMILIAL HYPERCHOLESTEROLEMIA IN THE MONGOLIAN POPULATION
Authors: Unurjargal Tsolmon , Byambatsogt Bolortuul , Sodovsuren Naranchimeg , Lhagvasuren Sodnomtsogt
Published: April 2021

Objective:

The objective of this study was to characterize LDLR (low density lipoprotein receptor) gene mutation in patients with familial hypercholesterolemia.

Design and method:

Methods: This cross-sectional study was included subjects aged from 20 to 64 years, with a clinical diagnosis of familial hypercholesterolemia. Clinical diagnosis of familial hypercholesterolemia was based on Dutch Lipid Clinic Network diagnostic criteria. Possible and probable familial hypercholesterolemia were defined as a total score was 3–5 and 6–8 points. Ten ml of venous blood samples were collected from all the subjects and used for biochemical and genetic analysis. Deoxyribonucleic acid was isolated from peripheral blood samples and precise primers were designed for LDLR gene which includes 18 exons. Polymerize chain reaction test was followed by deoxyribonucleic acid sequence analysis.

Results:

Results: A total of 89 subjects included in the study of which, 32 (36%) were men and 57 (64%) were women. The mean age of the participants was 46.5 ± 7.8 years. In our study, we found the following 3 LDLR mutations: S265R mutation in Exon-6, C308Y mutation Exon-8 and V502 M mutation in Exon-10.

Conclusions:

Conclusion: This was the first study to identify genetic mutations in LDLR gene in Mongolia. We conclude that screening of family hypercholesterolemia among the Mongolian population is very important to identify individuals who are prone to develop the atherosclerotic cardiovascular disease.
THE VARIETY OF GENETIC DEFECTS EXPLAINS THE PHENOTYPIC HETEROGENEITY AND THE MODE OF TRANSMISSION OF FAMILIAL HYPERKALEMIC HYPERTENSION
Authors: Hureaux Marguerite , Marzukiewicz Stephanie , Vargas-Poussou Rosa , Jeunemaitre Xavier
Published: April 2021

Objective:

Familial Hyperkalemic Hypertension (FHHt) is a rare inherited form of arterial hypertension. Four genes are responsible for this disease, interacting together in the regulation of ion transport in the distal renal tubule. Whether the type of variants and mutated gene explains the large phenotypic heterogeneity and the different modes of transmission in FHHt has not been explored yet.

We report herein the experience of a referral centre based on 151 molecularly proven FHHt cases (82 probands, 69 relatives).

Design and method:

Patients with persistent hyperkalemia without renal failure, associated with metabolic acidosis, were genetically explored by Sanger sequencing and by new generation sequencing (NGS)Identified variants were confirmed and classified according to the American College of medical Genetics.

Clinical and biological data were analyzed based on “questionnaires” filled out by the prescribing physicians. Statistical analyzes were done using Kruskal-Wallis test and post hoc Dunn's multiple comparison tests using Prism V6.

Results:

We identified 16 families with 12 different CUL3 splice-site variants, 48 families with 37KLHL3 variants (13 in recessive form, 24 in dominant form), 4 families with 4 different WNK1 intron 1 deletions, 11 families with 6 variants in the WNK1 acidic motif and 4 families with 4 different variants in the WNK4 acidic and basic motifs (figure 1). De novo cases were mainly observed in the CUL3-related cases (9 out of 16), recessive cases were only observed in few KLHL3-related cases (13 out 48), whereas all others variants were transmitted in an autosomal dominant manner. The more severe and earlier cases were caused by KLHL3 homozygous variants and CUL3 heterozygous variants in this case associated with growth retardation. Patients with WNK1 acidic motif variants had a typical biological phenotype without hypertension conversely to WNK4 mutations affecting the same motif. Molecular familial screening of relatives allowed us to detect 69 positive cases. Whatever the causing gene, administration of hydrochlorothiazide was effective.

Conclusions:

This study reinforces the interest of a genetic screening in case of suspicion of FHHt to better orientate the medical care of the patient and his family
SEX DIFFERENCES IN THE GENETIC RISK FOR HYPERTENSION
Authors: Aittokallio Jenni , Kauko Anni , Vaura Felix , Suvila Karri , Cheng Susan , Niiranen Teemu
Published: April 2021

Objective:

The development of hypertension differs markedly between men and women. The genetic drivers of this difference have not been fully studied. Genome-wide polygenic risk scores (PRSs), consisting of data from up to 6 M single nucleotide polymorphisms have been shown to considerably improve hypertension risk prediction, particularly in early-onset disease. However, the sex differences in the ability of PRSs to predict hypertension has not been studied previously.

Figure Survival curves from Cox proportional hazards models illustrate the cumulative risk of hypertension by systolic blood pressure PRS categories in FinnGen for women and men. We observed 123 579 women and 95 213 men with 27 804 and 28 113 cases of incident hypertension, respectively.

Design and method:

Our study sample comprised 218792 FinnGen Study participants with lifetime register-based follow-up for incident hypertension (56% women, mean age 58 years). We used publicly available genome-wide association results from UK Biobank to compute sex-specific PRSs for systolic blood pressure. We categorized SBP PRS into five bins according to percentiles (<2.5, 2.5–20, 20–80, 80–97.5, > 97.5) and used middle bin as the reference. We used multivariable-adjusted Cox proportional hazards models to measure the association between the PRSs and incident hypertension.

Results:

The PRS was more strongly associated with incident hypertension in women than in men (Figure). The hazard ratios (HR) per 1 SD increase in PRSs were 1.42 (95% CI, 1.40–1.44) for women and 1.27 (95% CI, 1.26–1.29) with an interaction P-value of 4x10–29. The difference between women (HR, 1.56; 95% CI, 1.53–1.58) and men (HR, 1.35; 95% CI, 1.32–1.37) was even greater for early-onset hypertension (onset at age < 55 years). Men and women in the top 2.5 PRS percentile had 2.1-fold (95% CI, 2.0–2.3) and 1.8-fold (95% CI, 1.7–1.9) greater risks of developing hypertension than the reference group.

Conclusions:

The genetic risk of hypertension appears to be more distinctive in women than in men, which may reflect physiological differences starting already at an early age. These results emphasize the use of sex-specific PRSs in clinical prediction of hypertension.
ACCEPTABILITY AND FEASIBILITY OF USING DIETARY NITRATE AND FOLATE SUPPLEMENTATION FOR THE TREATMENT OF HYPERTENSION IN A RURAL TANZANIAN POPULATION
Authors: Prabhakar Meghna , Kandhari Navneet , Mmbaga Blandina , Rogathi Jane , Gray William , Paddick Stella-Maria , Walker Richard , Siervo Mario
Published: April 2021

Objective:

There is a substantial and growing burden of hypertension and hypertensive related disease in Tanzania. Low-cost and effective interventions are urgently needed. Little evidence is available on the use of inorganic nitrate and folate for treating hypertension in Africans. This study aims to assess the acceptability and feasibility of using nitrate supplementation in the form of beetroot juice and folate as a combined dietary intervention in a hypertensive Tanzanian population.

Design and method:

A three-arm, parallel, placebo controlled randomised clinical trial was conducted. Acceptability was assessed by one-to-one interviews, compliance and study retention rate. Trial assessments included clinic and ambulatory blood pressure measurements, electrocardiography, salivary samples, and blood samples.

Results:

Forty-eight participants were randomised for intervention. Forty-six participants completed the feasibility questionnaire. Twenty-six (57%) did not know what hypertension was and 37 (80%) had never heard of beetroot. Forty-two (91%) participants were happy to have the ambulatory blood pressure measurements repeated. All participants reported to have a >90% compliance to the dietary supplements.

Conclusions:

Awareness and knowledge of hypertension and the dietary interventions were low. Despite this, the interventions and protocol were well tolerated. This pilot shows that a dietary intervention of this nature is acceptable to this population, and that our study protocol can be feasibly used for a future trial in this setting.
NITRATE-RICH BEETROOT JUICE ALONE OR IN COMBINATION WITH FOLIC ACID REDUCES BLOOD PRESSURE IN HYPERTENSIVE TANZANIAN ADULTS: A DOUBLE-BLIND RANDOMIZED CONTROLLED TRIAL
Authors: Prabhakar Meghna , Kandhari Navneet , Shannon Oliver , Fostier William , Koehl Christina , Rogathi Jane , Temu Gloria , Stephan Blossam , Gray William , Paddick Stella Maria , Haule Irene , Mmbaga Blandina , Walker Richard , Siervo Mario
Published: April 2021

Objective:

In Sub-Saharan Africa, current management strategies are struggling to control the burgeoning hypertension epidemic. Dietary interventions such as inorganic nitrate and folate could represent alternative strategies for reducing blood pressure in this setting. This study aims to explore the effects of dietary inorganic nitrate supplementation alone or in combination with folic acid supplementation on blood pressure in a group of adult individuals with elevated blood pressure in Tanzania.

Design and method:

A placebo-controlled, double blind, randomized controlled trial (RCT) was conducted. Forty seven participants were randomly assigned to three conditions for a period of 60 days: 1) high-nitrate beetroot juice (∼400 mg nitrate) and folic acid (∼5 mg folate), 2) high-nitrate beetroot juice and placebo, 3) nitrate-depleted beetroot juice and placebo. Clinic and 24-hour ambulatory blood pressure, markers of nitric oxide production, and measurements of intervention compliance were obtained prior to and following the intervention period.

Results:

Resting clinic-based systolic blood pressure was significantly lower after 60 days of nitrate supplementation alone (p = 0.01). Both alone and combined nitrate + folate interventions had a significant effect on 24-Hour systolic blood pressure. After 60 days systolic blood pressure dropped by −10.8 ± 9.8 mmHg (p < 0.001) and −6.1 ± 13.2 mmHg (p = 0.03) in the nitrate alone and nitrate + folate groups, respectively. There was a significant decrease in 24-hour diastolic blood pressure in the nitrate alone group (−5.4 ± 5.0 mmHg, p = 0.04).

Conclusions:

Dietary inorganic nitrate, alone or in combination with folic acid, represents a potential nutritional strategy to lessen the hypertension epidemic in Sub-Saharan Africa. These findings support the rationale for future long-term investigations exploring the efficacy of dietary nitrate for lowering blood pressure and attenuating CVD risk in this setting.
PROVINCIAL-LEVEL CARDIOVASCULAR AND ALL-CAUSE MORTALITY BURDEN ATTRIBUTABLE TO HYPERTENSION IN CHINA
Authors: Kang Yuting , Wang Zengwu , Chen Zuo , Zhang Linfeng , Wang Xin , Zheng Congyi , Jiang Linlin , Shao Lan , Tian Ye
Published: April 2021

Objective:

Understanding disparities in the burden of cardiovascular and all-cause mortality attributable to hypertension is crucial to inform and improve hypertension control measures. In this report, we estimate the population attributable fraction (PAF) of cardiovascular mortality attributable to hypertension at the national and provincial levels in China.

Design and method:

The multivariable-adjusted RRs by cox regression using cohort study with more than 30,000 individuals, along with the national BP level from national study, were used to calculate the population attributable fractions (PAF). China Hypertension Survey, involving 458,273 participants from 262 selected counties by stratified multistage random sampling method was used to calculate the prevalence of different BP level. CVD events were defined as the incidence of fatal and non-fatal stroke, fatal and non-fatal coronary heart disease (CHD), heart failure, and other causes from CVD.

Results:

Of more than 30,000 individuals aged 35 years or older in the current study, over a mean of 4.8 years of follow up (143,314.6 person-years), we documented 571 cardiovascular events. Comparing with normal BP, prehypertension and hypertension increased more than 50% and 170% risk for CVD events. Nationally, the CVD events attributable to prehypertension, hypertension and elevated BP were 17.30%, 28.74% and 37.99%, respectively. The PAFs for elevated BP ranged from 44.06% in Tianjin to 31.59% in Qinghai, however. In 2016, about 687.68 thousand (95%CI: 670.89, 705.15) and 1.14 (95%CI: 1.11, 1.17) million cardiovascular deaths were derived from prehypertension and hypertension, respectively. The province with high socio-demographic Index (SDI), such as Shanghai, Beijing and Tianjin, all had relative lower CVD death numbers for hypertension, with less than 15 thousands CVD deaths attributable to hypertension. More than 17 thousands CVD deaths could been derived from controlled hypertension in Shandong, Henna and Hebei provinces.

Conclusions:

Elevated BP were related with excess CVD deaths. Geography heterogeneity exited among 31 provinces, with lower excess CVD deaths in high SDI provinces. Additional attention should be taken to reduce prehypertension, which are preferable to attend universal health.
DIFFERENCES IN HYPERTENSION PHENOTYPES BETWEEN AFRICANS AND EUROPEANS: ROLES OF INHERITANCE AND ENVIRONMENT
Authors: Faconti Luca , McNally Ryan , Farukh Bushra , Adeyemib Olusoji , Cruickshankc J. Kennedy , Wilkinson Ian , Chowienczyk Philip , Ojji Dike
Published: April 2021

Objective:

Hypertension phenotypes differ in Africans and white Europeans, with a greater prevalence of low renin salt-sensitive hypertension and greater predisposition to adverse cardiac remodelling in Africans.

We aim to elucidate roles of inheritance and environment in determining hypertension phenotypes in Africans born and resident in Nigeria (AA), sub-Saharan Africans living in the UK (AE) and white Europeans in the UK (EE).

Design and method:

469 hypertensive subjects in the UK and Nigeria were enrolled. Biochemistry, blood pressure, left ventricular structure (echocardiography) and 24 h urinary collections of sodium and potassium were measured

Results:

24-hour urinary sodium and potassium excretion were similar in AE and EE but lower in AA with a proportionately greater excretion of potassium compared to sodium in Africans resident in Europe compared to those in Africa (sodium excretion 46.9% greater in AE compared to AA and potassium excretion 109.8% greater in AE compared to AA, both P < 0.01) so that the ratio of sodium to potassium in the urine was higher in AA compared to both AE and EE. Plasma renin was lower in Africans irrespective of residency compared to white Europeans, but aldosterone was higher in Africans in Europe compared to those in Africa (466.15 ± 32.95 pmol/L vs 258.60 ± 17.42 pmol/L, P < 0.001). Left ventricular mass index adjusted for blood pressure was greatest in Africans in Europe (103.27 ± 2.32 g/m2) compared to those in Africa (89.28 ± 1.98 g/m2, P < 0.01) or white Europeans (86.77 ± 2.63 g/m2, P < 0.01). The difference between AE and AA was largely driven by a greater LV cavity size in AE compared to AA (difference in end diastolic diameter, 0.45 ± 0.056 cm, P < 0.001). Consequently, the RWT showed a trend to “eccentricity” moving from AA to AE.

Conclusions:

Both genetic and environmental differences contribute to phenotypic differences between Africans in Europe and white Europeans. A low renin state is predominantly genetically determined whereas higher aldosterone, related to higher potassium intake or another environmental factor, may contribute to greater LV mass in Africans in Europe.
TWO DECADE'S TRENDS IN HYPERTENSION AMONG URBAN ADULT POPULATION OF EAST INDIAN COMMUNITY: OBSERVATION FROM A LONGITUDINAL COHORT
Authors: Chakraborty Kaushik , Chakraborty Nilanjana , Mitra Ramendra Nath , Saha Angana , Chatterjee Papri , Manna Subhankar , Mitra Dipra
Published: April 2021

Objective:

Hypertension is one of the predominant major contributors of chronic disease burden among global non communicable diseases. The study evaluated trends in self-reported doctor diagnosed hypertension (DDH) and measured blood pressure (mBP) prevalence along with associated risk factors in an Indian urban population over 20 years.

Design and method:

Longitudinal cohort was established in 2001 with 3030 households based on the stratified multistage cluster sampling. Adult participants (N = 7275; Male = 3765, Female = 3510) were enrolled. Three household questionnaire surveys were performed in year 2001–02, 2011–12, 2018–19 with the same population size to determine DDH trend. Two representatives’ cross-sectional surveys were conducted (In 2014–15, n:5741, male = 2319, female = 3422; In 2018–19, n = 5741, male = 2204, female = 3537) to evaluate trends in hypertension based on the mBP value. Blood pressure and anthropometric data were also recorded according to the established protocol. mBP classification was derived from Joint National Committee (JNC-8) guideline.

Results:

Prevalence of DDH (%) in successive surveys increased from 9.70, 17.86, 22.67 and measured BP (%) among pre-hypertensive 32.12, 39.17, hypertension-stage1 14.41, 19.91, hypertension-stage2 7.05, 8.26 over the time. Gender specific prevalence of hypertension showed progressive rise of DDH [OR = 0.69, CI: 0.61,0.78, p < .0001]and mBP [In 2014, PreHTN: OR = 1.69, CI = 1.49, 1.91, p < .0001; HTNstg1: OR:1.43, CI = 1.22, 1.68, p < .0001, HTNstg2: OR = 1.44,CI = 1.17, 1.78, p = 0.0007; In 2018, PreHTN: OR = 2.04, CI = 1.79,2.32, p < .0001; HTNstg1: OR = 2.23, CI = 1.91,2.60, p < .0001; HTNstg2: OR = 1.948, CI = 1.58,2.40, p < .0001] in men when compared to women. Association of DDH with smoking [In 2001–02, OR = 0.62, CI = 0.52,0.74, p < .0001; In 2018–19, OR = 0.75, CI = 0.63, 0.90, p = .0020] and duration of sleep (>8 hrs.) [In 2001–02, OR = 0.71, CI = 0.61, 0.82, p < .0001; In 2018–19, OR = 1.18, CI = 1.01, 1.38, p = 0.0401] established. Trend revealed higher education was a lower risk of hypertension. Increasing trends were observed across all hypertension categories among obese compared to normal.

Conclusions:

In mBP group, HTNstg2 prevalence has increased marginally over 7 years, among remaining groups increasing prevalence trend was unequivocal. Most of the long-established reversible risk factors association prevalence also increasing. Higher education having lower risk may well suggest importance of increased awareness. A strategy to reverse the rising trend of the chronic disease burden is required.