The Influence of Maternal Obesity on Cell-Free Fetal DNA and Blood Pressure Regulation in Pregnancies with Hypertensive Disorders

Background and Objectives: obesity and blood pressure disorders are one of the main risk factors for antenatal, intra, postpartum, and neonatal complications. In preeclampsia (PE), the placental hypoxia leads to vascular endothelium dysfunction, cell necrosis, and apoptosis. This condition is associated with the release of free fetal DNA (cffDNA) circulating in plasma. The disturbance of the efficiency of vasodilatation and blood pressure regulation in PE can be confirmed by analyzing the apelin, salusin, and prosalusin. This study aimed to assess the influence of obesity on cffDNA, and the effectiveness of maintaining normal blood pressure in patients with preeclampsia and gestational hypertension. Material and Methods: the research material was blood serum and oral mucosa swabs, obtained from 168 patients. Pregnant women were divided into the following: a control group (C)—67 women; a gestational hypertension group (GH)—35 patients; a preeclampsia with obesity group (PE + O) (pre-gravid BMI > 30)—23 patients. The rest were lean preeclamptic women (PE)—66 patients—(pre-gravid BMI < 25 in 43 women). Results: the cffDNA was observed in 1.50% of women in the C group, in 2.45% in the GH group, but in 18.18% of lean patients with preeclampsia. The cffDNA was detected in 58% of obese pregnant women with PE. The greater the placental hypoxia was in preeclampsia, the less efficient the hypotensive mechanisms, according to an analysis of the studied adipokines. The prosalusin concentration was significantly lower in the PE group with cffDNA than in the PE group without it (p = 0.008). Apelin was higher in the PE group with cffDNA (p = 0.006) compared to other groups. The same results were also observed in the subgroup with obesity. Conclusion: in preeclamptic women, obesity seems to act as an additive factor of placental damage by means of the dysregulation of hypotensive mechanisms.

Abstract T6: Adipocyte Bardet-Biedl Syndrome 1 Gene Is Critical For Blood Pressure Regulation

Bardet-Biedl syndrome (BBS) proteins have emerged as critical regulators of various physiological functions including blood pressure. The presence of hypertension in BBS patients is consistent with the finding that BBS knockout mice exhibit increased renal sympathetic nerve activity and arterial pressure. However, the role and contribution of Bbs genes in various tissues such as adipose tissue to blood pressure regulation remains unclear. To address this, we generated a novel conditional knockout mouse that lacks the Bbs1 gene in adipocytes by breeding mice bearing floxed alleles of the Bbs1 gene (Bbs1 flox/flox ) with mice expressing Cre specifically in adipocytes (Adiponectin Cre mice). Cre-mediated recombination was verified by loss of Bbs1 expression in fat pads, but not in other tissues such as the kidneys, liver and skeletal muscle. Next, we assessed whether adipocyte Bbs1 gene deletion affects body weight and glucose homeostasis. Interestingly, no body weight phenotype was observed in both male and female Adipo Cre /Bbs1 flox/flox mice compared to their control littermates (males: 40.5±2.9 g vs 37.4±5.1 g; female: 27.7±4.0 g vs 27.5±3.6 g; 16 weeks old). However, insulin tolerance test uncovered impaired insulin-induced glucose clearance in both male and female Adipo Cre /Bbs1 flox/flox mice. Subsequently, we measured blood pressure and found that Adipo Cre /Bbs1 flox/flox mice have a remarkable increase in systolic blood pressure (130.4±11.2 mmHg) compared to the control littermates (119.1±4.5 mmHg, p <0.05). Finally, measurement of the expression of the renin-angiotensin system components revealed significantly elevated angiotensinogen mRNA (2.43±1.31 AU vs 1±0.72 AU, p <0.01) and angiotensin-converting enzyme mRNA (2.96±2.51 AU vs 1±0.95 AU, p <0.05) in peri-renal adipose tissue, but not in other fat pads such as brown and inguinal adipose tissues. Interestingly, gene expression of angiotensin receptor 1a was not significantly altered by Bbs1 gene deletion. Taken together, our findings demonstrate that Bbs1 gene in adipose tissue play an important role in the control of insulin sensitivity and blood pressure.

Medullary vasomotor center: a modern view of the structure, function and its role in arterial hypertension pathogenesis

The medullary centers of blood pressure regulation have been in the field of vision of both physiologists and doctors for a very long period of time. This is mainly due to the abundance of structures and interstructural interactions in the brain stem, involved in maintaining blood pressure. Advances in research technology open new opportunities these days to look at this problem from a different angle. Moreover, research of medullary centers of blood pressure regulation will make it possible to understand better the mechanisms of persistent increase in blood pressure, which will create the preconditions for the formation of new pathogenetically substantiated therapeutic approaches in the treatment of such a widespread and dangerous pathology as arterial hypertension. Therefore, the aim of this work was to analyze modern views about the structure and composition of the medullary vasomotor center, its functions and its role in the arterial hypertension development. To achieve this goal, the search by keywords: arterial hypertension, baroreflex, NTS, DMN, RVLM, CVLM, CPA, SHR, LC and analysis of scientific articles from the databases of search engines Google Scholar, Web of Science, Pub Med was done. Conclusions: 1. The analysis of literature sources showed that the concept of "medullar vasomotor center" includes a number of brainstem formations, the most studied of which are the structures of the dorsal complex of the vagus nerve (the nucleus of the solitary tract, the dorsal motor nucleus, area postrema), the rostral and caudal ventrolateral regions of medulla, caudal pressor area, noradrenergic structures of the brainstem, in particular the locus coeruleus, as the biggest of them. 2. According to literary sources, arterial hypertension is accompanied by the changes in the morphofunctional state of the above-mentioned structures. The most common mechanisms are violation of the neurotransmitter composition within the structure and the neuroinflammatory process.

Altered circulating Tregs and their functional cytokines in hypertensive patients with or without left ventricular hypertrophy

Background:Left ventricular hypertrophy (LVH) is the most common target organ damage in hypertension. In addition to the increased left ventricular afterload, immune injury participates in LVH pathogenesis. CD4+CD25+Foxp3+ regulatory T lymphocytes (Tregs) are a T cell subset with immunomodulatory effects; abnormal Treg numbers or functions can cause immune disorders. This study aimed to explore the role of Tregs in LVH by investigating circulating Tregs and associated cytokine levels in hypertensive patients with LVH.Methods:Blood samples were collected from 69 healthy individuals (control group, CG), 91 hypertensive patients with LVH (LVH group) and 83 hypertensive patients without LVH (essential hypertension, EH group). Circulating Tregs and associated cytokines were measured by flow cytometry and enzyme-linked immunosorbent assays, respectively.Results:Circulating Tregs were significantly lower in EH and LVH patients than in CG subjects. The circulating Treg level was lower in LVH patients than in EH patients. No correlation between blood pressure regulation and Treg levels was found in EH or LVH patients. Furthermore, circulating Tregs in postmenopausal females were lower than those in males among LVH patients. Additionally, serum IL-10 and transforming growth factor (TGF)-β1 were decreased in EH and LVH patients, and the serum IL-6 level was significantly increased in LVH patients. Circulating Tregs were negatively correlated with CK, LDL, apoB, high-sensitivity C-reactive protein and left ventricular mass index values.Conclusion:Our study is the first to demonstrate the significantly decreased circulating Treg proportion in LVH patients. The protective effect of Tregs in LVH is independent of blood pressure regulation. The functional Treg cytokines IL-6, IL-10 and TGF-β1 participate in this immunomodulatory process.Trial registration: The study was approved by the Institutional Medical Ethics Committee of the Second Xiangya Hospital of Central South University (2018/No.046).