Unique Associations of DNA Methylation Regions With 24-Hour Blood Pressure Phenotypes in Blacks

Background: Epigenetic marks (eg, DNA methylation) may capture the effect of gene-environment interactions. DNA methylation is involved in blood pressure (BP) regulation and hypertension development; however, no studies have evaluated its relationship with 24-hour BP phenotypes (daytime, nighttime, and 24-hour average BPs). Methods: We examined the association of whole blood DNA methylation with 24-hour BP phenotypes and clinic BPs in a discovery cohort of 281 Blacks using reduced representation bisulfite sequencing. We developed a deep and region-specific methylation sequencing method, Bisulfite ULtrapLEx Targeted Sequencing and utilized it to validate our findings in a separate validation cohort (n=117). Results: Analysis of 38 215 DNA methylation regions (MRs), derived from 1 549 368 CpG sites across the genome, identified up to 72 regions that were significantly associated with 24-hour BP phenotypes. No MR was significantly associated with clinic BP. Two to 3 MRs were significantly associated with various 24-hour BP phenotypes after adjustment for age, sex, and body mass index. Together, these MRs explained up to 16.5% of the variance of 24-hour average BP, while age, sex, and BMI explained up to 11.0% of the variance. Analysis of one of the MRs in an independent cohort using Bisulfite ULtrapLEx Targeted Sequencing confirmed its association with 24-hour average BP phenotype. Conclusions: We identified several MRs that explain a substantial portion of variances in 24-hour BP phenotypes, which might be excellent markers of cumulative effect of factors influencing 24-hour BP levels. The Bisulfite ULtrapLEx Targeted Sequencing workflow has potential to be suitable for clinical testing and population screenings on a large scale.

Pathophysiological Mechanisms of Hypertension Development Induced by Fructose Consumption

During the past several decades, there has been a dramatic increase in fructose consumption worldwide in parallel with epidemics of metabolic diseases. Accumulating evidence has suggested that excessive fructose consumption...

Commentary on: Xbp1s-Ddit3, DNA damage and pulmonary hypertension

In this commentary, we discuss new observations stating that spliced X-box-binding protein 1 (Xbp1s)-DNA damage-inducible transcript 3 (Ddit3) promotes monocrotaline (MCT)-induced pulmonary hypertension (Jiang et al., Clinical Science (2021) 135(21), https://doi.org/10.1042/CS20210612). Xbp1s-Ddit3 is involved in the regulation of endoplasmic reticulum stress but is also associated with DNA damage repair machinery. Pathologic DNA damage repair mechanisms have emerged as critical determinants of pulmonary hypertension development. We discuss the potential relationship among Xbp1s-Ddit3, DNA damage, and pulmonary hypertension. Although Xbp1s-Ddit3 contributes to the regulation of cell proliferation and apoptosis and the development of vascular lesions, whether Xbp1s is a friend or foe remains controversial.

Vitamin D Deficiency Is a Potential Risk for Blood Pressure Elevation and the Development of Hypertension

Background and objectives: Hypertension is a global health problem and a major risk factor for cardiovascular diseases. Vitamin D deficiency is closely related to high blood pressure and the development of hypertension. This study investigated the relationship between the vitamin D and blood pressure status in healthy adults, and their 8-year follow-up was added. Materials and Methods: A total of 491 healthy middle-aged participants without any chronic illness, ages 21 to 67 at baseline, were divided into two groups as non-optimal blood pressure (NOBP) and optimal blood pressure (OBP). NOBP group was divided into two subgroups: normal (NBP) and high normal blood pressure (HNBP). Serum 25-hydroxy vitamin D levels were measured with the immunoassay method. 8-year follow-up of the participants was added. Results: The average vitamin D level was detected 32.53 ± 31.50 nmol/L in the OBP group and 24.41 ± 14.40 nmol/L in the NOBP group, and a statistically significant difference was found (p < 0.001). In the subgroup analysis, the mean vitamin D level was detected as 24.69 ± 13.74 and 24.28 ± 14.74 nmol/L in NBP and HNBP, respectively. Together with parathyroid hormone, other metabolic parameters were found to be significantly higher in the NOBP. During a median follow-up of 8 years, higher hypertension development rates were seen in NOBP group (p < 0.001). Conclusions: The low levels of vitamin D were significantly associated with NBP and HNBP. The low levels of vitamin D were also associated with the development of hypertension in an 8-year follow-up.

Fetal Undernutrition Programming, Sympathetic Nerve Activity, and Arterial Hypertension Development

A wealth of evidence showed that low birth weight is associated with environmental disruption during gestation, triggering embryotic or fetal adaptations and increasing the susceptibility of progeny to non-communicable diseases, including metabolic and cardiovascular diseases, obesity, and arterial hypertension. In addition, dietary disturbance during pregnancy in animal models has highlighted mechanisms that involve the genesis of arterial hypertension, particularly severe maternal low-protein intake (LP). Functional studies demonstrated that maternal low-protein intake leads to the renal decrease of sodium excretion and the dysfunction of the renin-angiotensin-aldosterone system signaling of LP offspring. The antinatriuretic effect is accentuated by a reduced number of nephron units and glomerulosclerosis, which are critical in establishing arterial hypertension phenotype. Also, in this way, studies have shown that the overactivity of the central and peripheral sympathetic nervous system occurs due to reduced sensory (afferent) renal nerve activity. As a result of this reciprocal and abnormal renorenal reflex, there is an enhanced tubule sodium proximal sodium reabsorption, which, at least in part, contributes directly to arterial hypertension development in some of the programmed models. A recent study has observed that significant changes in adrenal medulla secretion could be involved in the pathophysiological process of increasing blood pressure. Thus, this review aims to compile studies that link the central and peripheral sympathetic system activity mechanisms on water and salt handle and blood pressure control in the maternal protein-restricted offspring. Besides, these pathophysiological mechanisms mainly may involve the modulation of neurokinins and catecholamines pathways.

HYPERTENSION IN RELATION TO IMMUNE SYSTEM AND WAY OF LIFE ALONG WITH TREATMENT

The objective of the review is to explain the pathophysiology, different causes and various treatments involved in hypertension. This article discusses the disease's pathogenesis, etiology, diagnosis, and immunity. This review looks at the main significant epidemiological and clinical studies on the role of several lifestyle factors in hypertension development. This review examines the numerous mechanisms that cause hypertension in order to discover new treatments. In addition, it covers the many types of hypertension therapy. According to different studies, lifestyle habits may have an impact on blood pressure levels. Moreover, the importance of chronic inflammation in hypertension and its repercussions has been confirmed in genetically engineered mice lacking components of innate and/or adaptive immunity. Immune cell depletion enhances endothelial function, lowers oxidative stress, lowers the vascular tone, and protects against renal interstitial infiltrates, salt retention, and kidney injury. Based on existing literature, there is strong evidence that lifestyle variables can affect blood pressure levels. Then, in hypertensive people, lifestyle changes can help by lowering overall cardiovascular risk and death from any cause. The involvement of immunity as a common thread in the hypertension processes of many organ systems.

Obesity, Sodium Homeostasis, and Arterial Hypertension in Children and Adolescents

Background: The relationship between obesity, arterial hypertension, and excessive salt intake has been known for a long time; however, the mechanism of this relationship remains not clear. Methods: The paper presents a current literature review on the relationship between salt consumption and the development of arterial hypertension in children and adolescents with obesity. Results: In addition to the traditional theory of hypertension development due to the increase in intravascular volume and disturbances of sodium excretion, recent studies indicate the existence of a complex mechanism related to excessive, pathological secretory activity of adipocytes, insulin resistance, and impaired function of the renin–angiotensin–aldosterone axis. That makes obese children and adolescents particularly vulnerable to the development of salt-sensitive arterial hypertension. Studies performed in many countries have shown that children and adolescents consume more sodium than recommended. It is worth noting, however, that the basis for these recommendations was the extrapolation of data from studies conducted on adults. Moreover, more important than sodium intake is the Na/K ratio and water consumption. Conclusion: Regardless of the population-wide recommendations on reducing salt intake in children, specific recommendations for overweight and obese patients should be developed.

Clinical significance of 24-hour blood pressure monitoring in prediction of hypertension development in patients with gout

Aim. The aim of the study was to develop the model for establishing early diagnosis of hypertension in patients with gout. The model was based on data of 24-hour blood pressure monitoring.Material and Methods. A total of 69 patients with gout were enrolled in a single-stage cross-sectional prospective study. Three study groups were assigned as follows: group 1 (main group) comprised hypertensive men with gout (n = 41); group 2 (comparison group) comprised normotensive men with gout (n = 28); group 3 (control) included relatively healthy men (n = 30). Daily blood pressure monitoring was performed on an outpatient basis using a BPLab device (Peter Telegin, Russia).Results. The significant intergroup differences were found in the following parameters: lowest, mean, and highest 24-hour systolic blood pressure (SBP) values in patients of main and comparison groups (р < 0.001) and in patients of main and control groups (р < 0.001); mean and maximum 24-hour diastolic blood pressure (DBP) values in patients of main and comparison groups (р < 0.001) and in patients of main and control groups (р < 0.001); lowest, mean, and highest 24-hour pulse blood pressure (PBP) values in patients of main and comparison groups (р < 0.001) and in patients of main and control groups (р < 0.001); mean, and maximum 24-hour PBP values in patients of comparison and control groups (р < 0.001). Median values of the lowest, mean, and highest 24-hour SBP in hypertensive patients with gout were significantly higher than the corresponding values in normotensive patients with gout and healthy men of group 3 (p < 0.001). Median values of mean and maximum 24-hour DBP in main group were higher than the corresponding values in comparison group and control group (p < 0.001). Median values of the lowest, mean, and highest 24-hour PBP in hypertensive patients with gout exceeded the corresponding values of patients of control group (p < 0.001). Median values of the mean and maximum 24-hour PBP in main group exceeded the corresponding values of patients of comparison group (p < 0.001). Based on the binary logistic regression model, the prognostic algorithm for hypertension development in gout patients was created using the parameters of 24-hour blood pressure monitoring as predictors and the cut-off K value. If the value of K was > 0.54, then the hypertension development was predicted in gout patients. The sensitivity of developed diagnostic model was 0.84, and the specificity was 0.95.Conclusion. Тhe proposed model, based on the assessment of average-daily values of the lowest, mean, and highest SBP, allowed to establish early diagnosis of hypertension in patients with gout with the accuracy of up to 90%.

The Role of Short-Chain Fatty Acids of Gut Microbiota Origin in Hypertension

Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases, and its development involves multiple mechanisms. Gut microbiota has been reported to be closely linked to hypertension. Short-chain fatty acids (SCFAs)—the metabolites of gut microbiota—participate in hypertension development through various pathways, including specific receptors, immune system, autonomic nervous system, metabolic regulation and gene transcription. This article reviews the possible mechanisms of SCFAs in regulating blood pressure and the prospects of SCFAs as a target to prevent and treat hypertension.