Role of Perivascular Adipose Tissue in Vascular Physiology and Pathology

Blood pressure (BP) regulation is a complex homeostatic process involving multiple organ systems, including the cardiovascular, renal, and central and peripheral nervous systems.1 Inability to properly regulate BP can result in the development of hypertension, which is associated with an increased risk of stroke, myocardial infarction, and cardiac and renal failure,2–4 and is the leading determinant of risk of death worldwide.5 In addition to genetic and environmental factors known to play a role in the development of hypertension,6 body weight and obesity are highly correlated with hypertension in humans.7,8 This is particularly alarming given the increased prevalence of obesity, which now affects 1 in 3 people in the United States.9 The close association between obesity, hypertension, and other cardiovascular disorders suggests an important role for adipose tissue (AT) in the regulation of vascular tone and BP. Until the mid 1900s, AT was considered to be a form of connective tissue with the primary function of storing energy in the form of lipids.10 However, AT is now recognized to be an important endocrine organ that can secrete polypeptides and metabolites, known as adipokines, which are involved in the normal regulation of various physiological processes, including BP regulation and vascular function.10,11 In the setting of obesity, AT undergoes complex remodeling. This is marked by a significant increase in tissue mass, through adipocyte hyperplasia and hypertrophy. Changes in structural and cellular composition also occur, including changes in AT extracellular matrix, composition of lipid droplets, and infiltration of immune cells such as macrophages and lymphocytes, which results in low-grade inflammation.10,11 Most importantly, obesity shifts the secretory profile of AT, which in turn contributes to the dysregulation of BP and eventual development of hypertension.12 This is thought …