The role of inflammatory cytokines in endothelial dysfunction - PubMed (original) (raw)

Review

The role of inflammatory cytokines in endothelial dysfunction

Cuihua Zhang. Basic Res Cardiol. 2008 Sep.

Abstract

Clinical and experimental data support a link between endothelial dysfunction and inflammation. Inflammatory cytokines are important protagonists in formation of atherosclerotic plaque, eliciting effects throughout the atherosclerotic vessel. Importantly, the development of atherosclerotic lesions, regardless of the risk factor, e.g., diabetes, hypertension, obesity, is characterized by disruption in normal function of the endothelial cells. Endothelial cells, which line the internal lumen of the vasculature, are part of a complex system that regulates vasodilation and vasoconstriction, growth of vascular smooth muscle cells, inflammation, and hemostasis, maintaining a proper blood supply to tissues and regulating inflammation and coagulation. Current concepts suggest that the earliest event in atherogenesis is endothelial dysfunction, manifested by deficiencies in the production of nitric oxide (NO) and prostacyclin. The focus of this review is to summarize recent evidence showing the effects of inflammation on vascular dysfunction in ischemic-heart disease, which may prompt new directions for targeting inflammation in future therapies.

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Conflict of interest statement

Conflicts of Interest: None.

Figures

Fig. 1

The indicators of endothelial dysfunction in cardiovascular diseases (CVD) are portrayed. Normally, endothelial cells regulate the homeostasis of the vessel wall. The healthy endothelium is not leaky, anti-adhesive and is able to relax vascular smooth muscle cells. However, when risk factors (diabetes, ischemia/reperfusion, obesity and atherosclerosis etc.) disturb endothelial cells, which induce endothelial dysfunction and vascular remodelling. We have an impaired vascular control when the damaged endothelium is leaky, sticky and unable to relax vascular smooth muscle cells. In brief, central to the endothelial dysfunction is oxidative stress. The oxidative stress is induced by the production of reactive oxidative species (ROS) and this induces NF-κB. Key to the production of ROS is AGE/RAGE and TNF-α signaling, but ox-LDL/LOX-1 signaling is also involved in ROS production. The interactions among oxidative stress, AGE/RAGE, TNF-α/TNFR and ox-LDL/LOX-1 are because oxidative stress induces NF-κB, and this transcription factor can induce AGE, TNF-α and ox-LDL expression; and TNF-α can induce RAGE and LOX-1 expression. Thus, the oxidative stress of diabetes, begets more oxidative stress, eventually inducing endothelial dysfunction, because of decreased bioavailability of nitric oxide (NO, due to the reaction between NO and O2 · −)

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The role of inflammatory cytokines in endothelial dysfunction - PubMed (original) (raw)