Evaluating the role of perivascular adipose tissue in hypertension: Secretome Analysis and Quantitative Proteomics.

Analía Lourdes Redondo

University of South Dakota

The vascular pathophysiology typically found in hypertension has been studied extensively from the point of view of endothelial cells, smooth muscle and more recently in the adventitia. Only a few studies focus on the role of Perivascular Adipose Tissue (PVAT) for hypertension, all of which have been completed in animals. Two consistent findings are shared by most of these studies: reduced mass of PVAT and decreased anti-contractile effects of PVAT. In Spontaneously Hypertensive Rats (SHR), in the model of hypertension induced by Angiotensin II and the DOCA-salt decreased adipocyte size was found. The total mass of PVAT is also reduced in the SHR animals as compared to normotensive rats (WKY). PVAT function is impaired in the aorta and mesenteric arteries from hypertensive and pre-hypertensive animals where the anti-shrink effect is diminished or lost. Some adipokines as visfatin leptin and resistin appear to act as a growth factor on Vascular Smooth Muscle Cells (VSMC) stimulating their proliferation and migration. While other, as adiponectin, diminish VSMC proliferation. This benefit is reduced in pathophysiologic conditions when circulating adiponectin is decreased. Furthermore, although not been directly demonstrated other products from PVAT such as Reactive Oxygen Species (ROS), angiotensin peptides and steroid hormones, could encourage VSMC, which further involve the PVAT as a new pathogenic factor in Cardiovascular Disease (CVD). Therefore, the main objective of this project is to investigate the role of PVAT in the development of hypertensive disease by analyzing with proteomics techniques, the secretion of PVAT proteins (secretomes), released by animals with established hypertension (SHR adults) and animals that have not yet developed hypertension (pre hypertensive SHR) and compared with normotensive control animals(WKY). Proteomics is a scientific discipline focussing on large-scale study of proteins and their functions. In addition to the classical proteomic techniques such as 1-D or 2-D gel based and chromatographic fractionations and protein identification using mass spectrometry, recent advancements in proteomic tools including protein microarrays, quantitative mass spectrometry and bioinformatics open new ways towards comprehensive studies. All these approaches are expected to enable mapping of the PVAT secretomes, including the detection of very low abundant yet highly potent growth factors and adipokines where the role of highly sensitive antibody-based techniques should not be neglected. The culture medium conditioned by PVAT could be a subject of intensive proteome profiling in the search for soluble factors, which would be applicable in better understanding the physiopathology of hypertension.