ReviewAdipocytokines in relation to cardiovascular disease
Introduction
Adipose tissue functions as an energy stock that fills when the organism has excess of energy and empties when access to energy is limited. In addition it functions as a cushion and insulator of the body [1]. The discovery of leptin first demonstrated that adipose tissue can also be considered as a huge gland that produces bioactive molecules acting as paracrine and endocrine hormones, the so called adipo(cyto)kines. The list of adipo(cyto)kines continues to grow to hundreds of factors [2], [3]. Some of these adipo(cyto)kines like leptin play a role in homeostasis of body weight by controlling food intake. More recently it has become clear that many adipo(cyto)kines are mediators in the “adipo-cardiovascular axis”, the cross talk between adipose tissues, the heart and the vasculature.
While a minimal amount of adipose tissue is essential for living, the excess of fat in obesity is detrimental and associated with a high cardiovascular mortality and morbidity. Both animal and clinical investigations suggest that inflammation and dysfunction of adipose tissue in obesity, resulting in aberrant production of adipo(cyto)kines, are key processes that link obesity to cardiovascular diseases. It should however be noted that the relationship between cardiovascular disease and adiposity is often not straight forward as evidenced by the so called “obesity paradoxes”, namely the observations that an increase in body fat mass does not always increase morbidity or mortality, that a decrease in excessive body fat does not always improve patient health and that an increase in body fat mass sometimes reduces morbidity or mortality [4]. In the last decade many research aimed to better understand the link between adipose tissue and the cardiovascular system. Several recent reviews have addressed in detail different aspects of this link [5], [6], [7], [8], [9], [10], [11], [12]. The present paper aims to provide a concise and general overview of the actual concepts, supplemented with the most relevant recent findings related to the intriguing relation between adipose tissue and cardiovascular diseases.
Section snippets
“Adiposopathy”
During positive caloric balance adipocytes become hypertrophied. Excessive hypertrophy causes “adiposopathy”, a pathologic adipose tissue that creates adverse paracrine, endocrine and immune responses which may promote cardiovascular diseases, either directly or indirectly by stimulating major cardiovascular risk factors such as type-2 diabetes mellitus, high blood pressure or dyslipidemia [13]. The dysfunction of adipose tissue is a key link between obesity and cardiovascular disease.
Adipocytokines and endothelial dysfunction
Endothelial cells are connected through specialized structures which provide the primary endothelial barrier function. Endothelial dysfunction due to breakdown of the barrier promotes atherogenesis as a result of enhanced permeability through the endothelial layer, increased adherence of leukocytes, monocytes and macrophages and subendothelial accumulation of cholesterol-bearing lipoproteins.
Adiponectin reduces TNFα-stimulated expression of endothelial adhesion molecules and monocyte
Adipo(cyto)kines and hypertension
Many adipo(cyto)kines have vasoactive properties and therefore can influence blood pressure. It has been shown that lipoatrophic mice, born without white fat tissue, have a markedly decreased amount of perivascular adipose tissue, increased arterial pressure and compromised vascular function [47].
Adipo(cyto)kines and atherosclerosis
The importance of adipo(cyto)kines in the atherosclerotic process is nicely illustrated by the observation that transplantation of visceral adipose tissue into apolipoprotein E−/− mice caused a marked acceleration of atherosclerosis by inducing the production of pro-inflammatory factors [69].
The ability of many adipo(cyto)kines to stimulate angiogenesis is beneficial for adipose tissue growth, but less interesting in atherosclerosis as induction of endothelial cell proliferation and migration
Adipo(cyto)kines and heart diseases
Under normal conditions, epicardial and pericardial adipose tissues are local energy sources for the contractile activity of the heart by releasing fatty acids through lipolysis. However, expanded epicardial fat and pericardial fat are important risk factors for obesity-related cardiac dysfunction [89].
Many experimental studies demonstrate that adiponectin acts directly on cardiomyocytes to protect the heart from ischemic injury, hypertrophy, cardiomyopathy and systolic dysfunction [90]. These
Concluding remarks (Fig. 1)
The combat against cardiovascular diseases is challenged by the escalating global epidemic of obesity (“globesity”) and excess adipose tissue. Adipose tissues secrete adipo(cyto)kines that activate many different pathways in various cell types that regulate the cardiovascular circulatory system. These adipo(cyto)kines can exert opposite effects on cardiac and vascular functions. It is the sum of these functional changes that ultimately will determine the overall impact on the cardiovascular
Conflict of interest
Disclosure: no conflict of interest.
Acknowledgments
This work was supported by grants from FWO-Vlaanderen, the Bijzonder Onderzoeksfonds (BOF) of Ghent University and Geconcerteerde Onderzoeks Actie (GOA) of Ghent University.
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