Adipose tissue and vascular inflammation in coronary artery disease

Table 1 Possible link of resistin, C-reactive protein and apelin with vascular inflammation, atherosclerosis and cardiovascular diseas

Adipokine	Modulation of inflammation	Association with CVD
Leptin	↑ T cell activation and Th lymphocyte response ↑ cytokine release ↑ NK cell activation ↑ macrophages’ cytokine release Activates neutrophils ↑ chemotaxis ↑ oxidative stress ↑ CRP production from endothelium	↑ blood pressure ↑ atherothrombosis: ↑ cholesterol accumulation in vessel wall ↑ adhesion molecules (ICAM, VCAM) expression ↑ endothelial dysfunction (increasing eNOS production, ↓ NO, ↑ET-1) ↑ proliferation and migration of EC and VSMC ↑ ROS accumulation ↑ VSMC apoptosis ↓ angiogenesis ↑ platelet activity ↓ fibrinolysis ↑ PAI-1 ↑TF release from mononuclear cells Induce insulin resistance
Adiponectin	↓ T cell activation and proliferation ↓ NF-κB Increases IL-10 Inhibits CRP and IL-6 release	Associated with HDL-C and inversely with LDL-C ↓ atherothrombosis: ↓ ICAM-1, VCAM-1, and E-selectin ↓ Transformation of macrophages to foam cells ↓ vascular muscular smooth cells proliferation and migration ↑ TIMP, through the increase in IL-10 ↑ oxidation of free fatty acids in several tissue ↑ insulin sensitivity

CVD: Cardiovascular disease; CRP: C-reactive protein; EC: Endothelial cells; ET-1: Endothelin-1; ICAM: Intercellular adhesion molecule; HDL-C: High density lipoprotein cholesterol; IL: Interleukin; LDL-C: Low density lipoprotein cholesterol; NF-κB: Nuclear factor κB; NK: Natural killer; NO: Nitric oxide; PAI-I: Plasminogen activator inhibitor-I; TF: Tissue factor; TIMP: Tissue inhibitor of metalloproteinase; VCAM: Vascular cell adhesion molecule; VSMC: Vascular smooth muscle cells.

Table 2 Possible link of resistin, C-reactive protein and apelin with vascular inflammation, atherosclerosis and cardiovascular disease

Adipokine	Modulation of inflammation	Association with CVD
Resistin	↑NFκB dependent cytokine release and adhesion molecule expression (including TNF-α/IL-6) on endothelial cells ↑ proliferation of vascular smooth muscle cells through ERK and PI3K pathways	Endothelial dysfunction: ↓ NO and EDHF ↑ ET-1 release ↑ VEGF and MMP ↑ expression of adhesion molecules and chemokines ↓ TRAF-3 Controversial effects in humans on insulin resistance and type 2 diabetes
CRP	↑ expression of ICAM, VCAM, E selectin recruitment of mononuclear cells through MCP 1 VSMC proliferation, migration ↑ CD4+ LymphocitesT ↑ gamma – INF production ↑ ET-1 release ↑ CD40/CD40L on endothelium ↑ complement activation	↑ endothelial dysfunction through ↓ NO vasodilatation ↑ oxidized LDL opsonization and macrophages uptake with subsequent foam cells formation ↑ in vessel wall oxidative stress ↑ TF and PAI 1 ↑ MMP
Apelin	↓ superoxide radicals ↓ NADPHO ↓ oxidative injury ↑ NO ↑ vascular progenitor cells mobilization	↑ inotropism ↑ neoangiogenesis ↓ endothelial dysfunction↓ Ang II and BP ↓ myocardial damage after infarction ↑ cholesterol efflux from macrophages

Ang: Angiotensin; BP: Blood pressure; CRP: C-reactive protein; CVD: Cardiovascular disease; EDHF: Endothelium-derived hyperpolarizing factor; ERK: Extracellular signal-regulated kinase; ET-1: Endothelin-1; HDL-C: High density lipoprotein cholesterol; ICAM: Intercellular adhesion molecule; IL: Interleukin; INF: Interferon; LDL-C: Low density lipoprotein cholesterol; MCP: Monocyte chemoattractant protein; MMP: Metalloproteinase; NADPHO: Nicotinamide adenosine dinucleotide phosphate oxidase; NO: Nitric oxide; PI3K: Phosphatidylinositol-3-kinase; TF: Tissue factor; TNF: Tumor necrosis factor; TRAF: Tumor necrosis factor receptor-associated factor; VCAM: Vascular cell adhesion molecule; VEGF: Vascular endothelial cell growth factor; VSMC: Vascular smooth muscle cells.