Elsevier

Atherosclerosis

Volume 227, Issue 2, April 2013, Pages 216-221
Atherosclerosis

Review
Adipokines as mediators of endothelial function and atherosclerosis

https://doi.org/10.1016/j.atherosclerosis.2012.12.029Get rights and content

Abstract

For many decades, adipose tissue was considered as an inactive body compartment that was only used as an energy store. During the recent years, an increasing amount of data has revealed that adipose tissue is a major endocrine and paracrine organ producing numerous enzymes, hormones and growth factors which are collectively termed as adipokines. Several experimental and clinical studies showed that adipokines modulate insulin sensitivity and have an influence on glucose/fat metabolism and obesity. Apart from these properties, recent research revealed several direct actions of adipokines on endothelial function, vascular homeostasis and atherogenesis which are independent of their effects on glucose and fat metabolism.

The present review focuses on the direct effects of adipokines on vascular/endothelial function and atherosclerosis and summarizes the experimental and clinical data which suggest a role for these molecules as potential diagnostic and prognostic cardiovascular markers as well as potential therapeutic target to reduce cardiovascular risk.

Introduction

For many decades, adipose tissue had been considered as an inert body compartment whose only role was the thermal insulation of the body and energy storage in the form of triacylglycerols. However, during the recent years adipose tissue has been acknowledged as a major endocrine and paracrine organ that produces hundreds of proteins e.g. adiponectin, leptin, resistin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), atrial natriuretic peptide and angiotensinogen [1], [2]. These molecules are known under the term “adipokines” and, contribute as enzymes, hormones or growth factors in the modulation of insulin resistance and metabolism of fats and glucose (Table 1), and therefore have an indirect effect on atherosclerosis. In addition, they also exert direct actions on endothelial function, vascular homeostasis and atherogenesis (Fig. 1). The epidemic of obesity and cardiovascular diseases during the last century has lead to intense research on the role of adipokines in obesity and atherosclerosis and their use as potential therapeutic targets to reduce cardiovascular morbidity and mortality.

This review focuses on the direct effects of adipokines on the endothelial function and atherogenesis, and discusses the available evidence which supports their use as potential diagnostic and prognostic cardiovascular markers as well as potential therapeutic targets to reduce cardiovascular risk. The main actions on vascular functions of the adipokines not included in the present review are summarized in the Supplemental Table.

Section snippets

Leptin

Leptin, a 16 kDa adipokine which is coded by the ob(Lep) gene in chromosome 7, modulates energy intake and expenditure, lipid metabolism, hematopoiesis, thermogenesis and the function of pancreatic β cells and ovaries [3], [4]. The molecular signaling of leptin is summarized in Fig. 2. A role of leptin in liver diseases either in alcoholic or non-alcoholic liver disease and chronic viral diseases of the liver has also been described [5], [6], [7].

Leptin acts on receptors of the endothelium and

Concluding remarks

This review focuses on the direct effects of adipokines on vascular/endothelial function and atherogenesis. It is evident that there is an increasing amount of experimental and clinical data which reveal a direct effect of adipokines on vascular function and atherogenesis that is independent of their effects on insulin sensitivity and glucose/fat metabolism. These associations raise the issue of potentially using these molecules as diagnostic and prognostic cardiovascular markers, as well as

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