Essential role of perivascular adipose tissue in blood pressure regulation

血管周围脂肪组织在血压调节中的重要作用

基本信息

批准号：
8670864
负责人：
Lin Chang
金额：
$ 38.88万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8670864
关键词：
Abdomen Address Adipocytes Adipose tissue Affect Angiotensin II Angiotensinogen Animal Model Antihypertensive Agents Aorta Atherosclerosis Binding Biological Assay Biology Blood Pressure Blood Vessels Boxing Cardiac Cardiovascular Diseases Cells Chest Circadian Rhythms Clinical Research Crossbreeding Data Development Dimensions Drops Exhibits Fatty acid glycerol esters Figs - dietary Framingham Heart Study Functional disorder Genetic Transcription Goals Homeostasis Hormones Human Hypertension Hypotension In Vitro Knock-out Knockout Mice Lead Literature Losartan Maintenance Messenger RNA Modeling Mus Muscle PPAR gamma Pattern Peripheral Peroxisome Proliferator-Activated Receptors Phase Physiological Physiology Plasma Publishing Rattus Regulation Renin Renin-Angiotensin System Reporting Resting Phase Role Saphenous Vein Smooth Muscle Myocytes Stroke Testing Tissue Donors Transcriptional Regulation Transgenic Mice Transgenic Organisms Vascular Diseases Vascular Endothelial Cell Visceral Work adipokines autocrine base blood pressure regulation constriction in vivo internal thoracic artery loss of function mouse model novel diagnostics novel therapeutic intervention overexpression prevent promoter public health relevance receptor suprachiasmatic nucleus uncoupling protein 1 vasoconstriction

项目摘要

DESCRIPTION (provided by applicant): Perivascular adipose tissue (PVAT), which surrounds most vessels, produces undetermined or less characterized factors that could target endothelial cells and vascular smooth muscle cells, and herein contribute to the maintenance of vessel homeostasis. Also, PVAT is de facto a distinct functional vascular layer actively contributing to vascular function and dysfunction. The Framingham Heart Study supports that PVAT volume is associated with higher thoracic and abdominal aortic dimensions, suggesting that PVAT contributes to aortic remodeling. Loss of PVAT in mice are hypotensive during resting phase, which leads to dipper blood pressure, but a physiological relationship between PVAT and regulation of blood pressure and the possible underlying mechanisms remains to be addressed. Angiotensinogen, one of components of renin angiotensin system, is produced in adipocytes and regulates blood pressure through autocrine manner. However, extensive preliminary data here show angiotensinogen expression in PVAT in a circadian rhythm manner, which is higher in active phase and lower in resting phase. The proposed project will test the central hypothesis that PVAT is critical to maintain blood pressure in resting phase, and local angiotensinogen in PVAT is one of predominant molecules that regulates blood pressure in resting phase taking advantage of newly developed unique animal models lacking PVAT, gain- and loss-of-function approaches in vivo and in vitro, and assessment of blood pressure and PVAT physiology and function with physiologically relevant experimental approaches. The aims of this proposal are: 1). Define a critical role of PVAT on blood pressure regulation in resting phase; 2). Determine whether hypotension in mice lacking PVAT is due to angiotensinogen deficiency; and 3). Determine the mechanisms of circadian rhythm regulation of angiotensinogen in PVAT and the effects on blood vessel tone. The results of this proposal will have profound implications on the understanding of PVAT biology and hypertension in cardiovascular diseases.

描述（由申请人提供）：围绕大多数血管的血管周围脂肪组织（PVAT）产生不确定的或更少的特征因素，这些因素可能靶向内皮细胞和血管平滑肌细胞，而这里有助于维持血管稳态。同样，事实上，PVAT是一个独特的功能性血管层，积极促进血管功能和功能障碍。 Framingham心脏研究支持PVAT量与较高的胸腔主动脉尺寸和较高的胸腔主动脉尺寸有关，这表明PVAT有助于主动脉重塑。在静息阶段，小鼠的PVAT损失是降压性的，这导致了北极亚血压，但是PVAT与血压调节之间的生理关系以及可能的潜在机制尚待解决。血管紧张素原质是肾素血管紧张素系统的组成部分之一，是在脂肪细胞中产生的，并通过自分泌方式调节血压。然而，这里的广泛初步数据显示，昼夜节律方式在PVAT中表达了血管紧张素的表达，在活性相中较高，在静息阶段较低。拟议的项目将检验中心假设，即PVAT对于在静息阶段保持血压至关重要，而PVAT中的局部血管紧张素原是主要分子之一，它是一种主要的分子，它在静止阶段中调节血压的静止阶段利用了新开发的独特动物模型，缺乏PVAT，增益和功能障碍方法，并与血液和PVAT的功能和PVAT相关的功能和PVAT的相关性和PVAT的功能相关性，方法。该提议的目的是：1）。定义PVAT在静息阶段调节血压调节的关键作用； 2）。确定缺乏PVAT的小鼠的低血压是否是由于血管紧张素的缺乏症。和3）。确定PVAT血管紧张素原和对血管张力的影响的昼夜节律节奏调节的机制。该提案的结果将对对PVAT生物学和心血管疾病中的高血压的理解具有深远的影响。