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High-Carbohydrate Diet Enhanced the Anticontractile Effect of Perivascular Adipose Tissue Through Activation of Renin-Angiotensin System.

ABSTRACT: The perivascular adipose tissue (PVAT) is an active endocrine organ responsible for release several substances that influence on vascular tone. Increasing evidence suggest that hyperactivation of the local renin-angiotensin system (RAS) in the PVAT plays a pivotal role in the pathogenesis of cardiometabolic diseases. However, the local RAS contribution to the PVAT control of vascular tone during obesity is still not clear. Since the consumption of a high-carbohydrate diet (HC diet) contributes to obesity inducing a rapid and sustained increase in adiposity, so that the functional activity of PVAT could be modulated, we aimed to evaluate the effect of HC diet on the PVAT control of vascular tone and verify the involvement of RAS in this effect. For that, male Balb/c mice were fed standard or HC diet for 4 weeks. Vascular reactivity, histology, fluorescence, and immunofluorescence analysis were performed in intact thoracic aorta in the presence or absence of PVAT. The results showed that HC diet caused an increase in visceral adiposity and also in the PVAT area. Phenylephrine-induced vasoconstriction was significantly reduced in the HC group only in the presence of PVAT. The anticontractile effect of PVAT induced by HC diet was lost when aortic rings were previously incubated with angiotensin-converting enzyme inhibitor, Mas, and AT₂ receptors antagonists, PI3K, nNOS, and iNOS inhibitors, hydrogen peroxide (H₂O₂) decomposing enzyme or non-selective potassium channels blocker. Immunofluorescence assays showed that both Mas and AT₂ receptors as well as nNOS and iNOS isoforms were markedly expressed in the PVAT of the HC group. Furthermore, the PVAT from HC group also exhibited higher nitric oxide (NO) and hydrogen peroxide bioavailability. Taken together, these findings suggest that the anticontractile effect of PVAT induced by HC diet involves the signaling cascade triggered by the renin-angiotensin system through the activation of Mas and AT₂ receptors, PI3K, nNOS, and iNOS, leading to increased production of nitric oxide and hydrogen peroxide, and subsequently opening of potassium channels. The contribution of PVAT during HC diet-induced obesity could be a compensatory adaptive characteristic in order to preserve the vascular function.

SUBMITTER: Dos Reis Costa DEF

PROVIDER: S-EPMC7845559 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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High-Carbohydrate Diet Enhanced the Anticontractile Effect of Perivascular Adipose Tissue Through Activation of Renin-Angiotensin System.

Dos Reis Costa Daniela Esteves Ferreira DEF Silveira Ana Letícia Malheiros ALM Campos Gianne Paul GP Nóbrega Natália Ribeiro Cabacinha NRC de Araújo Natália Ferreira NF de Figueiredo Borges Luciano L Dos Santos Aggum Capettini Luciano L Ferreira Adaliene Versiani Matos AVM Bonaventura Daniella D

Frontiers in physiology 20210115

The perivascular adipose tissue (PVAT) is an active endocrine organ responsible for release several substances that influence on vascular tone. Increasing evidence suggest that hyperactivation of the local renin-angiotensin system (RAS) in the PVAT plays a pivotal role in the pathogenesis of cardiometabolic diseases. However, the local RAS contribution to the PVAT control of vascular tone during obesity is still not clear. Since the consumption of a high-carbohydrate diet (HC diet) contributes t ...[more]

PMID: 33519529

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Project description:During hypertension, vascular remodeling allows the blood vessel to withstand mechanical forces induced by high blood pressure (BP). This process is well characterized in the media and intima layers of the vessel but not in the perivascular adipose tissue (PVAT). In PVAT, there is evidence for fibrosis development during hypertension; however, PVAT remodeling is poorly understood. In non-PVAT depots, mechanical forces can affect adipogenesis and lipogenic stages in preadipocytes. In tissues exposed to high magnitudes of pressure like bone, the activation of the mechanosensor PIEZO1 induces differentiation of progenitor cells towards osteogenic lineages. PVAT's anatomical location continuously exposes it to forces generated by blood flow that could affect adipogenesis in normotensive and hypertensive states. In this study, we hypothesize that activation of PIEZO1 reduces adipogenesis in PVAT preadipocytes. The hypothesis was tested using pharmacological and mechanical activation of PIEZO1. Thoracic aorta PVAT (APVAT) was collected from 10-wk old male SD rats (n=15) to harvest preadipocytes that were differentiated to adipocytes in the presence of the PIEZO1 agonist Yoda1 (10 µM). Mechanical stretch was applied with the FlexCell System at 12% elongation, half-sine at 1 Hz simultaneously during the 4 d of adipogenesis (MS+, mechanical force applied; MS-, no mechanical force used). Yoda1 reduced adipogenesis by 33% compared with CON and, as expected, increased cytoplasmic Ca2+ flux. MS+ reduced adipogenesis efficiency compared with MS-. When Piezo1 expression was blocked with siRNA [siPiezo1; NC=non-coding siRNA], the anti-adipogenic effect of Yoda1 was reversed in siPiezo1 cells but not in NC; in contrast, siPiezo1 did not alter the inhibitory effect of MS+ on adipogenesis. These data demonstrate that PIEZO1 activation in PVAT reduces adipogenesis and lipogenesis and provides initial evidence for an adaptive response to excessive mechanical forces in PVAT during hypertension.

Dataset Information

High-Carbohydrate Diet Enhanced the Anticontractile Effect of Perivascular Adipose Tissue Through Activation of Renin-Angiotensin System.

Publications

High-Carbohydrate Diet Enhanced the Anticontractile Effect of Perivascular Adipose Tissue Through Activation of Renin-Angiotensin System.

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