ReviewAdipokines as mediators of endothelial function and atherosclerosis
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
References (101)
- et al.
Alterations of leptin during IFN-alpha therapy in patients with chronic viral hepatitis
Journal of Hepatology
(2006) - et al.
EDHF: new therapeutic targets?
Pharmacological Research: The Official Journal of the Italian Pharmacological Society
(2004) - et al.
Glucose-dependent regulation of cholesterol ester metabolism in macrophages by insulin and leptin
The Journal of Biological Chemistry
(2002) - et al.
Leptin treatment inhibits the progression of atherosclerosis by attenuating hypercholesterolemia in type 1 diabetic Ins2(+/Akita):apoE(−/−) mice
Atherosclerosis
(2012) - et al.
Leptin and coronary heart disease: prospective study and systematic review
Journal of the American College of Cardiology
(2009) - et al.
Adipocyte-derived cytokine resistin causes endothelial dysfunction of porcine coronary arteries
Journal of Vascular Surgery
(2005) - et al.
Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway
Biochemical and Biophysical Research Communications
(2005) - et al.
Increased serum levels of interleukin-1beta in the systemic circulation of patients with essential hypertension: additional risk factor for atherogenesis in hypertensive patients?
The Journal of Laboratory and Clinical Medicine
(1997) - et al.
Resistin, acute coronary syndrome and prognosis results from the AtheroGene study
Atherosclerosis
(2007) - et al.
Prognostic significance of plasma resistin levels in patients with atherothrombotic ischemic stroke
Clinica Chimica Acta; International Journal of Clinical Chemistry
(2007)