Leptin in Atherosclerosis: Focus on Macrophages, Endothelial and Smooth Muscle Cells

Abstract

Increasing adipose tissue mass in obesity directly correlates with elevated circulating leptin levels. Leptin is an adipokine known to play a role in numerous biological processes including regulation of energy homeostasis, inflammation, vascular function and angiogenesis. While physiological concentrations of leptin may exhibit multiple beneficial effects, chronically elevated pathophysiological levels or hyperleptinemia, characteristic of obesity and diabetes, is a major risk factor for development of atherosclerosis. Hyperleptinemia results in a state of selective leptin resistance such that while beneficial metabolic effects of leptin are dampened, deleterious vascular effects of leptin are conserved attributing to vascular dysfunction. Leptin exerts potent proatherogenic effects on multiple vascular cell types including macrophages, endothelial cells and smooth muscle cells; these effects are mediated via an interaction of leptin with the long form of leptin receptor, abundantly expressed in atherosclerotic plaques. This review provides a summary of recent in vivo and in vitro studies that highlight a role of leptin in the pathogenesis of atherosclerotic complications associated with obesity and diabetes.

Role of Epicardial Adipose Tissue in Cardiovascular Diseases: A Review

“…The decreased adiponectin expression attenuates endothelial function and leads to increased tumor necrosis factor-α (TNF-α) production, which increases inflammation and oxidative stress. The increased leptin level promotes adhesion of monocytes, macrophage-to-foam cell transformation, and unfavorable changes in lipid and inflammatory cytokine levels in adipose tissue [28]. All these processes result in the development and destabilization of atherosclerotic plaques [29].…”

Screening of Bovine Tissue-Specific Expressed Genes and Identification of Genetic Variation Within an Adipose Tissue-Specific lncRNA Gene

“…Among the 16 protein-coding genes, LEP gene encodes leptin (a peptide hormone), which plays an important role in regulating energy metabolism, homeostasis, endocrine, immunity, inflammatory response and reproduction. Mutations in the LEP gene are linked to diseases such as obesity and type II diabetes ( 28 ). Five genes are transmembrane proteins, including ADIG, GIPR, SLC2A4, HCAR1 , and LHCGR .…”

Immature Vascular Smooth Muscle Cells in Healthy Murine Arteries and Atherosclerotic Plaques: Localization and Activity

“…In nestin-GFP mice, we find a small number of nestin-positive cells in perivascular fat only. The amount of leptin receptor increases in atherosclerotic lesions [22], and many studies demonstrate lesion-promoting properties of leptin (data reviewed in [23]). In healthy murine arteries, we find leptin receptors only in perivascular fat, which indicates that leptin does not promote atherosclerosis via NG2 + CD146 + cells.…”