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

Priya Raman,Saugat Khanal

doi:10.3390/ijms22115446

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.

Highlights

Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA; School of Biomedical Sciences, Kent State University, Kent, OH 44240, USA
We previously reported that leptin, at concentrations relevant to obesity and diabetes, has a direct stimulatory effect on the proatherogenic matricellular protein, thrombospondin-1 (TSP-1), implicated in atherosclerosis
Previous studies have shown that murine macrophages isolated from leptindeficient ob/ob mice exhibit reduced cholesterol accumulation and lower inflammatory response, revealed via attenuated CD36, MHC Class II, CD11b, CD40 and SR-A expression [83]. These results have suggested that leptin deficiency decreases foam cell formation and inhibits development of atherosclerosis

Summary

Introduction

Cardiovascular disease (CVD) is the leading cause of death world-wide accounting for 18.6 million deaths in 2019, a number expected to increase to greater than 23.6 million by 2030 [1]. A plethora of studies have revealed that the adipose tissue, white adipocytes, secrete numerous proteins collectively known as the ‘adipokines’ with varied endocrine functions [14]. Such adipocyte-secreted proteins play an important role in the regulation of glucose and fatty acid metabolism, energy homeostasis, inflammatory responses as well as control of blood pressure [14,15,16,17]. While the current literature has many excellent reviews discussing the contribution of different adipokines in the etiology of obesity and related metabolic and cardiovascular disorders, the role of leptin in pathogenesis of atherosclerosis has been somewhat conflicting. The current review attempts to provide an overview of recent in vivo and in vitro studies highlighting the involvement of leptin in pathogenesis of atherosclerotic complications associated with obesity and diabetes

Clinical Studies

Animal Studies

Leptin and Macrophages

Effect

Leptin and Vascular Smooth Muscle Cells

Conclusions