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.
The role of the physiology of the perivascular adipose tissue in regulation of blood pressure remains to be determined. We will address this void using unique animal models and physiologically relevant functional assays with the ultimate goal of promoting the development of novel diagnostic and therapeutic approaches to manage cardiovascular disease.
|Xiong, Wenhao; Zhao, Xiangjie; Villacorta, Luis et al. (2018) Brown Adipocyte-Specific PPAR? (Peroxisome Proliferator-Activated Receptor ?) Deletion Impairs Perivascular Adipose Tissue Development and Enhances Atherosclerosis in Mice. Arterioscler Thromb Vasc Biol 38:1738-1747|
|Qi, Xiao-Yan; Qu, Shun-Lin; Xiong, Wen-Hao et al. (2018) Perivascular adipose tissue (PVAT) in atherosclerosis: a double-edged sword. Cardiovasc Diabetol 17:134|
|Chang, Lin; Xiong, Wenhao; Zhao, Xiangjie et al. (2018) Bmal1 in Perivascular Adipose Tissue Regulates Resting-Phase Blood Pressure Through Transcriptional Regulation of Angiotensinogen. Circulation 138:67-79|
|Xiong, Wenhao; Zhao, Xiangjie; Garcia-Barrio, Minerva T et al. (2017) MitoNEET in Perivascular Adipose Tissue Blunts Atherosclerosis under Mild Cold Condition in Mice. Front Physiol 8:1032|
|Chang, Lin; Garcia-Barrio, Minerva T; Chen, Y Eugene (2017) Brown Adipose Tissue, Not Just a Heater. Arterioscler Thromb Vasc Biol 37:389-391|
|Zhang, Weizhen; Chang, Lin; Zhang, Chao et al. (2015) Central and peripheral irisin differentially regulate blood pressure. Cardiovasc Drugs Ther 29:121-7|
|Meng, Zhuo-Xian; Wang, Lin; Chang, Lin et al. (2015) A Diet-Sensitive BAF60a-Mediated Pathway Links Hepatic Bile Acid Metabolism to Cholesterol Absorption and Atherosclerosis. Cell Rep 13:1658-69|
|Zhang, Weizhen; Chang, Lin; Zhang, Chao et al. (2015) Irisin: A myokine with locomotor activity. Neurosci Lett 595:7-11|
|Villacorta, Luis; Chang, Lin (2015) The role of perivascular adipose tissue in vasoconstriction, arterial stiffness, and aneurysm. Horm Mol Biol Clin Investig 21:137-47|
|Brown, Nicholas K; Zhou, Zhou; Zhang, Jifeng et al. (2014) Perivascular adipose tissue in vascular function and disease: a review of current research and animal models. Arterioscler Thromb Vasc Biol 34:1621-30|