PVAT mediated immunomodulation in vasculo-adipose balance in atherosclerosis

Abstract

Atherosclerosis is a chronic inflammatory disease characterized by endothelial dysfunction, lipid deposition and inflammatory infiltration [1]. Endothelial dysfunction/injury caused by high shear stress promotes initiation of atherosclerosis, followed by subsequent adhesion of circulating inflammatory cells to the dysfunctional endothelium. These processes are further aggravated by accumulation of cholesterol in the arterial wall and lead to atherosclerosis [2]. One of the identified features of endothelial cells in response to local inflammation is dedifferentiation and switching of endothelial-to-mesenchymal transition which may be involved in the loss of endothelial phenotypes towards unspecialized mesenchymal-like cells that could undergo redifferentiation into mesodermal cell types, including adipocytes, in response to local inflammation [3]. This process can be triggered by various inflammatory cytokines and TGF-β which are produced in inflamed adipose tissue [4]. Adipose tissues play a significant role in atherosclerosis progression and are broadly classified as white adipose tissue (WAT) and brown adipose tissue (BAT). Initial studies have supported the hypothesis that dysfunctional WAT might be positively associated with atherosclerosis development, whereas activation of BAT may protect against atherosclerosis development. A third type beige adipose tissue (BeAT), has also been identified which is characterized by high expression of the brown adipocyte marker uncoupling protein-1 (UCP-1) [5].