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）产生可靶向内皮细胞和血管平滑肌细胞的未确定或特征较少的因子，并且在此有助于维持血管稳态。此外，PVAT 实际上是一种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 体积与较高的胸主动脉和腹主动脉尺寸相关，表明 PVAT 有助于主动脉重塑。小鼠PVAT损失在静息期会导致低血压，从而导致血压升高，但PVAT与血压调节之间的生理关系以及可能的潜在机制仍有待解决。血管紧张素原是肾素血管紧张素系统的组成部分之一，由脂肪细胞产生，通过自分泌方式调节血压。然而，这里大量的初步数据显示PVAT中血管紧张素原的表达呈昼夜节律方式，在活动期较高，在静息期较低。拟议的项目将测试以下中心假设：PVAT 对于维持静息期血压至关重要，PVAT 中的局部血管紧张素原是利用新开发的缺乏 PVAT 的独特动物模型调节静息期血压的主要分子之一，增益体内和体外功能丧失方法，以及通过生理相关实验方法评估血压和 PVAT 生理学和功能。该提案的目标是：1）。明确 PVAT 对静息期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原缺乏所致；和3）。确定 PVAT 中血管紧张素原的昼夜节律调节机制及其对血管张力的影响。该提案的结果将对心血管疾病中PVAT生物学和高血压的理解产生深远的影响。