bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANGIOTENSIN II MODULATES MONOCYTE-TO-MACROPHAGE DIFFERENTIATION: EFFECT ON THP-1-LIKE MACROPHAGE CELL PHENOTYPE, POLARIZATION AND REACTIVE OXYGEN SPECIES GENERATION
Authors: Barhoumi Tlili , Boudjellal Mohammad , Mahmud Azra 
Published: April 2021

Objective:
Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension, a highly prevalent cardiovascular(CV) risk factor associated with increased CV morbidity and mortality. One of the main effector cells in innate immune response are macrophages and several studies have reported their implication in pathophysiology of hypertension. In the vasculature and kidney, macrophage-derived reactive oxygen species (ROS) and inflammatory cytokines cause endothelial dysfunction, resulting in vascular oxidative stress and impairment of sodium excretion. Furthermore, angiotensin (Ang) II infusion is known to induce hypertension and vascular damage, particularly endothelial dysfunction, inflammation and oxidative stress. Renin angiotensin system (RAS) stimulation triggers monocyte activation and migration. ROS and cytokines secreted by macrophages can modulate blood pressure(BP) by triggering vascular endothelial dysfunction. Angiotensin II receptors are expressed in immune cells like T cells and monocytes. The aim of our study was to explore the effect of angiotensin II on THP-1-like macrophage cell phenotype, polarization and ROS generation.

Design and method:
THP-1-like macrophage cells were incubated with Ang II (100 nM) for 48 h. Cell phenotype analysis was performed using flow cytometry after intracellular and extracellular staining with CD11c, CD64, CD206, HLA-DR, CD116 and TNFa. We determined the effect of Ang II stimulation on ROS generation by macrophages using Cell Rox kit; viability and apoptosis using immunofluorescence and cell phenotyping using flow cytometry.

Results:
There was a significant increase in ROS generation in cells incubated with Ang II compared with control. Ang II induces THP-1-like macrophage polarization by increasing HLA-DR, CD11c and TNFa and decreasing CD206 markers. Ang II significantly increases apoptosis in a time-dependent fashion from 24 to 72-h and changed cell CD inflammatory markers after 24-h incubation.

Conclusions:
Differences in ROS generation, phenotype and polarization of THP-1-like macrophage cells in presence of Ang-II may underlie the role of monocyte/macrophages in vascular inflammation. The downstream pathways may be a potential therapeutic target for ang-II induced inflammation and vascular damage in hypertension.
REGIONAL AORTIC VASCULAR DYSFUNCTION IN A RODENT MODEL OF METABOLIC SYNDROME
Authors: Ameer Omar Ziad , Salman Ibrahim M , Alwadi Aiman Yahya 
Published: April 2021

Objective:
Obesity and diabetes constitute a hallmark of metabolic syndrome that is directly linked to vascular dysfunction and high blood pressure (BP). Accordingly, we aimed to investigate regional functional changes in thoracic and abdominal aortic responses in a rat model of high fat diet (HFD) and streptozotocin (STZ)-induced diabetes mellitus.

Design and method:
Five weeks old male Wistar Albino rats (n = 24) were fed with either HFD (45 kcal% fat) or control diet (10 kcal% fat) for 10 weeks. At 10 weeks of age, 40 mg/kg STZ and saline were injected intraperitoneally into the HFD and control groups, respectively. At the end of the treatment, rats were euthanized to assess vasoconstrictor and vasodilator responses of dissected aortic segments.

Results:
Conscious tail-cuff systolic BP was higher in the HFD relative to control (154 ± 6 mmHg vs. 110 ± 4 mmHg, p < 0.001). Oral glucose tolerance test (oGTT) generated greater AUCs in the HFD rats relative to controls (64,361 ± 383 vs. 14,169 ± 398, p < 0.001). Abdominal aortic vasoconstriction (N/g) to norepinephrine (NE, 1E-9 – 3E-5 M) and the depolarizing signals of high potassium (KCl, 5 – 120 mM) was greater (p < 0.05) in the HFD group compared with controls. Thoracic aortic vasoconstrictor responses (N/g) to NE, but not KCl, were greater (p < 0.05) in the HFD group as compared to controls. Abdominal, but not thoracic, endothelium-dependent vasorelaxation to acetylcholine (1E-10 – 1E-5 M) was blunted (p < 0.05) in the HFD group relative to controls. In contrast, thoracic and abdominal aortic responses to sodium nitroprusside (SNP)-induced endothelium-independent relaxation remained comparable between groups.

Conclusions:
Vascular functional responses are altered along the descending aorta in metabolic syndrome, exhibiting exaggerated vasocontractility and impaired endothelium-dependent relaxation. These vascular functional abnormalities could potentially underlie the development of hypertensive cardiovascular disease associated with the metabolic syndrome.
GENOME-WIDE ASSOCIATION STUDY FOR PHARMACOGENETIC RESPONSE OF BLOOD PRESURE TO BETA BLOCKER AND CALCIUM CHANNEL BLOCKER DRUGS
Authors: Warren Helen , Garofalidou Tatiana , Singh Sonal , Melander Olle , Hiltunen Timo , Glorioso Nicola , Cooper-Dehoff Rhonda , Dominiczak Anna , Caulfield Mark , Padmanabhan Sandosh , Munroe Patricia 
Published: April 2021

Objective:
There is substantial inter-individual variability in blood pressure (BP) responses to anti-hypertensive drugs and it is hypothesised that there could be genetic influences. One goal of pharmacogenetics is to aid in treatment selection. However very few variants have been identified. After the success of genome-wide association studies (GWAS) for BP, it is hoped GWAS could also reveal genes associated with BP treatment response.

Design and method:
A discovery analysis was performed including participants from ASCOT and NORDIL studies. Six different analyses were performed for systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) responses to monotherapy beta blockers (BBs) and calcium channel blockers (CCBs).
BP response was defined as post-treatment BP minus baseline BP. All analyses adjusted for age, sex, baseline BP and principal components. ASCOT analyses were also adjusted for dose and previous antihypertensive use, and excluded patients taking either BB/CCB drug at baseline, whereas NORDIL participants were previously untreated and subsequently treated on the same drug dose.
Genotyped data was imputed to 1000 Genomes, testing ∼7million common variants. Results from ASCOT and NORDIL were meta-analysed, with total N = 2,556 for BBs and N = 3,369 for CCBs.
Any variants reaching P < 1 × 10-5 for SBP and DBP response to BBs were tested for replication in available ICAPS consortium data (N = 1,328).

Results:
Strong correlation between baseline BP and BP response shows patients with higher BP have greater BP reduction post-treatment.
No variants reached genome-wide significance in any of the GWAS analyses, and none replicated in ICAPS data.
Lookups of ∼1,000 published BP-associated variants were performed, but none reached Bonferroni significance level. Ongoing analyses are testing BP genetic risk scores for association with treatment response.
Comparison of GWAS results shows correlation between SBP vs DBP response (r2 = 0.48) and SBP vs PP response (r2 = 0.76), but none between response to BBs vs CCBs.

Conclusions:
Despite being the largest GWAS of antihypertensive response, we found no significant associations, showing that larger studies are still required to increase power for discoveries. Model comparisons show different genes are likely to influence response to different antihypertensive drugs, with different genetic architecture.
RELATION BETWEEN APOLIPOPROTEIN E GENE POLYMORPHISM AND LIPID SPECTRUM IN HYPERTENSIVE PATIENTS
Authors: Varahabhatla Sai Krishna Ragh , Buryak Viktor 
Published: April 2021

Objective:
To study the relationship between apolipoprotein E gene polymorphism and lipid spectrum modification in hypertensive patients.

Design and method:
We examined 310 hypertensive patients (177 males and 133 females) ages 56,11 ± 0,68 years and history duration 6,51 ± 0,48 years, who were administrated with any antihypertensive components and no any specific lipid-lowering medications. According to office blood pressure measurement the average brachial value was 141,33 ± 1,34/87,62 ± 0,79 mmHg. The lipid spectrum components and apolipoprotein E gene polymorphism were assessed using automatic clinical biochemical analyzer «Cobas c311» and amplifier for single nucleotide polymorphism identification «Thermal Cycler CFX96TM Real-Time PCR Detection Systems» accordingly. Statistical data were presented like mean ± standard error and 95% confidence interval. Statistically significant difference was considered in case of P < 0,05.

Results:
The average values of total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoproteins (VLDL), triglycerides and indices of atherogenicity was 5,18 ± 0,08 mmol/l [5,02–5,34], 1,32 ± 0,03 mmol/l [1,27–1,37], 3,06 ± 0,07 mmol/l [2,92–3,2], 0,79 ± 0,02 mmol/l [0,75–0,83], 1,74 ± 0,05 mmol/l [1,64–1,83] and 3,21 ± 0,08 [3,05–3,38] respectively. Apolipoprotein E polymorphism was presented with alleles E2 (n = 41, 13,26%), E3 (n = 291, 93,87%) and E4 (n = 95, 30,65%) as well. Based on single nucleotide polymorphism identification there were defined next variants of genotypes: E2/E2- rarest of all genotypes (n = 2, 0,65%), E2/E3 (n = 34, 10,97%), E2/E4 (n = 5, 1,61%), E3/E3 (n = 179, 57,74%), E3/E4 (n = 78, 25,16%) and E4/E4 (n = 12, 3,87%). This way, it was found the domination of homozygous variants (n = 193, 62,26%). Besides that, overwhelming majority of them had both E3 allele and, as a result, E3/E3 genotype (n = 179, 92,75%). More over, this trend was independent of age and gender affiliation, but full spectrum of genotypes was inherent only for elderly patients (n = 105, 33,87%).

Conclusions:
The course of arterial hypertension reflects the mild degree of activity (isolated systolic hypertension) of the disease. Arterial hypertension associated with mixed-dyslipidemia (type 2b). Apolipoprotein E gene polymorphism is characterized by a wide range of alleles and genotypes among the hypertensive population. In hypertensive subjects the most common allele is E3 as well as genotype – is E3/E3 (opposite to E3/E4 in case of heterozygous variant).
HYPERURICEMIA AND TELOMERE LENGTH IN SUBJECTS WITH NEW CASES OF HYPERTENSION ACCORDING TO THE 10-YEAR PROSPECTIVE STUDY
Authors: Podpalova Olga , Generalov Igor , Podpalov Vladislav , Babenko Andrei , Kolyadko Marina , Mrochek Aleksandr 
Published: April 2021

Objective:
To reveal the association of high level of serum uric acid and telomere length in 10-year prospective study using the data from Belarusian national representative survey.

Design and method:
In 2007/2008 a 10-year prospective analysis of 3500 randomized individuals living in a district of Vitebsk started (coverage of the survey was 97.9%). In 2012/2013 there was a second screening of this population (coverage of the survey was 84.3%) respectively. In 2017/2018 a 10-years prospective analysis included subjects with newly diagnosed hypertension in the second screening. Examination of these patients included standard questionnaires for detection of cardiovascular risk factors, measurements of blood pressure, blood chemistry, electrocardiography, echocardiography, ultrasound examination of brachiocephalic vessels, real-time PCR for the detection telomere length of peripheral blood lymphocytes.

Results:
We examined population of 2171 persons with normal blood pressure and 1257 persons with hypertension in 2007/2008. 286 new cases of hypertension developed in 5 years (14,4% of men and 12,2% of women). According to multifactorial regression analysis we revealed significant positive relationship between the frequency of new cases of hypertension and IV quartile of serum uric acid level (339–527 mmol/l) (df = 1; c2Wald = 5,1; p < 0,05) as well as other risk factors, adjusted for age and sex. Regression analysis of 170 randomized subjects showed that the IV quartile of uric acid level (339–527 mmol/l), determined at first screening, was associated with the I quartile of telomere length in 10 years in subjects with newly diagnosed hypertension adjusted for age and sex (df = 1; c2Wald = 4,9; p < 0,05).

Conclusions:
Level of serum uric acid > = 339 mmol/l was a risk factor for the development hypertension in 5 years in randomized urban population and detection of lower level of telomere length in 10 years in persons with new cases of hypertension.
AGT, ACE, AGTR1, UMOD AND ADIPOQ GENES POLYMORPHISMS INTERACTIONS IN PREHYPERTENSION
Authors: Simicevic Livija , Josipovic Josipa , Milicic Borna , Djacic Kresimir , Domislovic Viktor , Gelemanovic Andrea , Jelakovic Ana , Zivka Dika , Karanovic Sandra , Bozina Tamara , Lovric Jasna M. , Jelakovic Bojan 
Published: April 2021

Abstract

Objective:
Prehypertension (PHT) is recognized as a cardio-renal risk factor, and associated with progression to hypertension (HT). Studies of the genetic background of PHT have not been fully elucidated and the results suggested a possible role of genes involved in the etiopathogenesis of HT. The lack of data has prompted this study to hypothesize that hypertension and metabolic syndrome-related AGT rs2004776, ACE rs1799752, AGTR1 rs5186, UMOD rs13333226, ADIPOQ rs266729 and rs17300539 gene polymorphisms are more commonly found in subjects with PHT, than in subjects with optimal and normal blood pressure (BP).

Design and method:
A total of 601 subjects were included in this cross-sectional, observational study; 319 with high normal BP (PHT, 120–139/80–89 mmHg), ages 20–45, and 282 individuals with normal and optimal BP as a control group (NT).

Results:
The results indicated that the AGT, ACE, AGTR1, UMOD, and ADIPOQ gene polymorphisms were not found more frequently in PHT subjects than in NT. A significant difference was found in the number of rs266729 ADIPOQ heterozygous carriers; there were less carriers in the PHT group (35.1%) than in the NT group (44.7%), P < 0.03. The significance of the heterozygous model (CG vs GG/CC) of rs266729 ADIPOQ polymorphism in PHT in terms of reduced risk was observed (OR 0.66; 95% CI 0.47–0.92; P = 0.01). PHT was significantly associated with following haplotypes: hIAGCA ACE:UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729:AGTR1 (OR 1.56; 95%CI 1.08–2.24; P = 0.02), hIAGC ACE:UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729 (OR 1.45; 95%CI 1.07–1.96; P = 0.02), hIAG ACE:UMOD:ADIPOQ_rs17300539 (OR 1.30; 95%CI 1.00–1.68; P = 0.05), hAGC UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729 (OR 1.37; 95%CI 1.07–1.77; P = 0.01) and hAG UMOD:ADIPOQ_rs17300539 (OR 1.42; 95%CI 1.07–1.90; P = 0.02). Results emphasized two significant models of gene-gene-other determinants interactions with PHT, one model included creatinine, total cholesterol, alpha-1-microglobulin, ADIPOQ rs17300539 and UMOD rs13333228; and the second model includes ADIPOQ rs17300539, AGT rs2004776, cardiovascular risk, sex, BMI, and the gene-gene interaction AGTR1:ADIPOQ_rs266729:UMOD:ACE.

Conclusions:
The finding of five significantly related gene-gene interactions, as well as the discovery of their haplotypes that increase the PHT risk, and the finding of two gene-gene-other determinants interactions models, confirmed the good selection of genes, particularly UMOD and ADIPOQ, involved in various biological pathways responsible for controlling BP.
LIDDLE SYNDROME – DETECTION OF NOVEL MUTATION IN A FAMILY WITH HYPERTENSION
Authors: Filipovsky Jan , Mares Stepan , Pesta Martin , Hrabak Jaroslav 
Published: April 2021

Abstract

Objective:
Liddle syndrome is a rare monogenic form of arterial hypertension with autosomal dominant inheritance. It is caused by mutation of genes coding one of three subunits of epithelial sodium channel (ENaC), which is located in distal nephron. Under physiological conditions, its expression and activity is regulated to maintain fluid and electrolytes homeostasis by reabsorbing Na+. Mutated channel cannot be degraded and therefore, it is accumulated on cell membrane; this results in enhanced sodium reabsorption. The most common clinical presentation of Liddle syndrome is early onset of hypertension, hypokalemia, suppressed plasma renin activity and low plasma aldosterone level. Up to now, 36 mutations causing Liddle syndrome were described.

Design and method:
Genetic assessment was performed in a Czech family of three generations (n = 14, see Figure) where hypertension and tendency to hypokalemia was present in several members. We used PCR amplification of specific alleles of SCNN1B and SCNN1G genes which was followed by Sanger sequencing.

Results:
We present a novel mutation causing Liddle syndrome: Tyr604∗ in beta-subunit of epithelial sodium channel. This mutation is supposed to generate a premature stop codon at position 604, resulting in truncated beta-subunit of EnaC. It was found in 7 members of the family: I-1, II-1 and 2, and III-1 to 4. Phenotypes of these subjects were different: from severe hypertension and hypokalemia (subjects I-1 and III-3, manifestation in 10 and 5 years, respectively) to normotension with normal potassium levels (III-1 and 2, now aged 8 and 10 years, respectively); however, all the seven subjects with mutation had hypoaldosteronism (serum level < 0.13 ng/ml).

Conclusions:
A new mutation causing Liddle syndrome is described. It is manifested with different severity and mild forms that are not manifested in early childhood exist; thus, Liddle syndrome may be more frequent among adult hypertensive subjects than currently supposed. Proper diagnosis is important as the patients respond well to treatment with ENaC blocker amiloride.
ASSOCIATION OF ARTERIAL STIFFNESS WITH AGT, ACE, NOS3, TNF, MMP9, CYBA POLYMORPHISM IN HEALTHY ADULTS
Authors: Akopyan Anna , Kirillova Karina , Turchina Tatiana , Samokhodskaya Larisa , Strazhesko Irina , Orlova Iana 
Published: April 2021

Abstract

Objective:
Arterial stiffness (AS) is a prominent risk factor for cardiovascular diseases. It is known that different polymorphisms are associated with cardiovascular diseases, while there is insufficient evidence that genetic traits lead to arterial wall changes, including AS. The aim of this study was to find the association between increased AS and polymorphisms that are associated with cardiovascular diseases and are involved in renin-angiotensin-aldosterone system, chronic inflammation and oxidative stress in healthy adults.

Design and method:
We investigated 153 healthy adults, mean age 50.56 ± 13.14 years, 35% male, 22% smokers. Increased AS was defined as pulse wave velocity (PWV) > 10 m/s. Measurements were performed by applanation tonometry using SphygmoCor device (AtCor, Australia). Insulin resistance was diagnosed if HOMA IR was > 2,5. Leucocyte telomere length (LTL) were measured by real-time PCR. AGT, ACE, NOS3, TNF, MMP9 polymorphisms were detected by real-time PCR using DNA technologies (Russia) standard kits, and CYBA polymorphism was detected by Applied Biosystems (USA) standard kit. Associations of genotypes and alleles with increased PWV were studied using chi-square or Fisher's exact test. Multiple logistic regression models were created to identify the effect of genotype and risk factors on PWV.

Results:
Increased AS was associated with D-allele (OR = 1.89, 95% CI: 1.16–3.12, p = 0.014) and DD-genotype (OR = 3.42, 95% CI: 1.39–9.36, p = 0.005) of ACE Ins > Del polymorphism. ACE Ins > Del polymorphism predicted increased AS along with sex, age and LTL. The results of multiple logistic regression analysis are represented in the table.

Conclusions:
In healthy adults increased AS is strongly associated with DD-genotype of ACE polymorphism, sex, age and leucocyte telomere length
HYPERTENSION CAUSED WITH LONG-TERM UNCONTROLLED USING OF NASAL DECONGESTANTS. HOW SAFE ARE OVER-THE-COUNTER DRUGS FOR SELF-MEDICATION?
Authors: Schelkanovtseva Ekaterina , Ermolaev Alexander , Mironova Olga 
Published: April 2021

Objective:
Elevated blood pressure is known to increase the cardiovascular risks. High blood pressure (BP) can be both a consequence of incorrect drug use and other forms of hypertension. Over-the-counter (OTC) drugs can carry a potential risk, but still in a number of countries the OTC drugs can be bought without a doctor‘s prescription.

Design and method:
A 46-year-old man presented with headache, palpitation, high BP of 160/100 mmHg. These symptoms worsened during last month. The patient was working as a coal miner for 23 years. Bad habits: smoking for 10 years with pack of cigarettes a day. He was diagnosed essential hypertension five years ago and asthma four years ago. He referred to a physician. Mono-therapy of losartan 25 mg twice a day was prescribed, but there was no persistent effect of it. Physical examination: BMI 30.7 kg/m2, office BP 150/100 mmHg, heart rate 92/minute. By chemistry: creatinine 109.11 mkmol/l, GFR 95.4 ml/min (CKD-EPI), total cholesterol 3,86 mmol/l, triglycerides 3.09 mmol/l, HDL 0.88 mmol/l, VLDL 1.4 mmol/l, LDL 1.4 mmol/l. Blood count with a normal range. Ambulatory BP measurements for 24 hours on monotherapy of losartan: the mean pressure per day 143/87 mmHg, a non-dipping BP profile. Both eyes hypertension retinopathy was revealed. He did not have a left ventricular hypertrophy on echocardiogram. The patient revealed the use of OTC nasal decongestants for 20 years to treat the presence of chronic nonallergic rhinitis. The patient was advised to exclude the nasal decongestants. The office BP was 115/80 mm/Hg in the morning and 125/85 mm/Hg in the evening since 10 days after exclusion of nasal drops.

Results:
A nasal septal deviation was recently revealed. Septoplasty led to successful reduce of his nasal symptoms. On follow-up visit the patient had normal BP level without any antihypertensive therapy.

Conclusions:
This clinical case demonstrates the importance of drug regulation and potential harm for the OTC drugs use by the general population without of medical appointments. Notably, the importance of using a proper talk with patients suffering hypertension and to suggest a questionnaire aimed at detection of secondary reasons.