Adipose tissue in the pathophysiology of cardiovascular disease: Who is guilty?

Table 1 Sources and potential role in cardiovascular disease of key adipokines

Adipokine	Primary source(s)	Potential role in CVD
Adiponectin	Adipocytes	↑Insulin sensitivity, energy consumption, fatty acid oxidation
		↓Oxidative stress
		Anti-inflammatory activity
		↓TNF-α, IL-6, interferon-c ↑IL-1R antagonist
		Modulation of chemokine expression
		Improved endothelial function
		eNOS induction ↑NO ↓ROS
		regulation of adhesion molecules
		Regulation of macrophage function
		Antiaggregants effects
		Decreased progression of atherosclerotic lesions
Leptin	Adipocytes	Appetite regulation and modulation of energy expenditure
		Independent prognostic marker of ACS
		Modulation of blood pressure
		Regulation of platelet aggregation and induction of arterial thrombosis
		TF, CRP and adhesion molecules induction in endothelial cells
		TF induction in peripheral blood mononuclear cells
		Maintenance of progression of atherosclerotic disease
Resistin/RELMs	RELM-α: Adipose tissue macrophages (human), adipocytes (mice)	Induction of insulin resistance
		Cell proliferation (RELM-β)
		Cytokine-like functionality (RELM-γ)
	RELM-β: Tumor and gastro-intestinal cells	Pro-inflammatory activity
		Independent predictive marker of atherosclerosis and severity of ischemic injury
	RELM-γ: Hematopoietic tissue	Effects on endothelial cells
		↑Adhesion molecules, cytokines, TF, plasminogen activator inhibitor, von Willebrand factor, endothelin
		↓e-NOS expression
		Smooth muscle cell proliferation and migration
TNF-α	Inflammatory cells, monocytes, macrophages, adipocytes	Reduction of insulin signaling
		Induction of insulin resistance
		Maintaining proinflammatory state and atherosclerosis
IL-6	Inflammatory cells, stromal vascular fraction cells, adipocytes, liver, muscle	Induction of insulin resistance
		Maintaining pro-inflammatory status
		Modulation of pro-inflammatory cytokines and pro-thrombotic mediators release
		Promotion of lipoproteins oxidation
		Activation of matrix metalloproteinase
		Induction of CRP production by the liver
Visfatin	Lymphocytes, macrophages, adipocytes, other cells	Monocyte chemotactic activity
		Endothelial dysfunction
		Atherosclerotic plaque destabilization
		TF induction
Other adipokines
Apelin	Adipocytes, stromal vascular cells and cardiac myocytes	Cardiomyocyte function regulation
Omentin	Stromal vascular cells of visceral adipose tissue	↑Insulin-stimulated glucose uptake in both Low levels in severe coronary atherosclerotic disease and arterial stiffness and carotid plaque in patients with diabetes
		Possible marker of metabolic dysfunction
Vaspin	Visceral and subcutaneous adipose tissue	Reduced plasma and mRNA levels in patients with unstable angina
		Low serum concentrations in patients with carotid atherosclerosis

ACS: Acute coronary syndrome; CRP: C-Reactive protein; eNOS: Endothelial nitric oxide synthase; IL: Interleukin; IL-1R: Interleukin-1 receptor; NO: Nitric oxide; RELM: Resistin like molecule; ROS: Reactive oxygen species; TF: Tissue factor; TNF: Tumor necrosis factor.