Endothelial Dysfunction in Coronary Artery Disease

Abstract

The endothelium is a physical barrier between the blood and vascular smooth muscle, a source of enzymes activating and deactivating cardiovascular hormones and a site of production of relaxing and contracting factors. In addition, the endothelium is a source of growth inhibitors and promoters of vascular smooth muscle cells. Monoaminooxidase deactivates catecholamines and serotonin. Angiotensin converting enzyme transforms angiotensin I into angiotensin II and breaks down bradykinin into inactive products. Nitric oxide is a potent vasodilator and inhibitor of platelet function that under most circumstances is released together with prostacyclin, which exerts similar effects. Both substances play an important protective role in the coronary circulation in that they cause continuous vasodilation and inhibition of platelet function. In addition, the endothelium is a source of contracting factors such as endothelin-1, thromboxane A2, and endoperoxides. Endothelium-derived growth inhibitors include heparin (sulfates) and transforming growth factor beta 1, while basic fibroblast growth factors and platelet-derived growth factor and possibly endothelin promote proliferation. Because of its strategic anatomic position, the endothelium is a primary target for injuries and cardiovascular risk factors. In particular, aging, low density lipoproteins, hypertension, diabetes, and ischemia alter endothelium function. In arterial coronary bypass grafts, the release of nitric oxide is more pronounced than in vein grafts. Alterations of endothelial function may contribute to vasospasm, thrombus formation, and vascular proliferation and in turn myocardial ischemia, all common events in patients with coronary artery disease.

Evidence of the Participation of Peribiliary Mast Cells in Regulation of the Peribiliary Vascular Plexus Along the Intrahepatic Biliary Tree

“…In normal and diseased livers, the hemodynamic regulation in the hepatic lobules is mainly conducted by perisinusoidal cells and endothelial cells by releasing ET and NO as effector molecules (Gondo et al, 1993;Leivas et al, 1998, Rockey et al, 1998. Regarding the hemodynamics around the intrahepatic biliary tree, the endothelium of PVP may take part in the regulation of vascular tone through the release of relaxing and contracting factors under basal conditions, and when activated by different stimuli, as has been speculated for other organs (Laffi and Marra, 1999;Luscher et al, 1993). The close topologic and numeric association of the peribiliary MC and the small vessels of PVP suggests that the peribiliary MC participate directly or indirectly in the regulation of these vessels by an autocrine and/or paracrine effect.…”

Evaluation of bioavailability of nitric oxide in coronary circulation by direct measurement of plasma nitric oxide concentration

“…However, bioavailability of NO is diminished in the subjects with a wide range of cardiac risk factors and pathologic conditions, such as aging, gender, smoking, hypertension, hypercholesterolemia, diabetes mellitus, hyperhomocystinemia, heart failure, infections, and polymorphisms of the endothelial NOS (15)(16)(17)(18)(19)(20)(21)(22)(23). Importantly, endothelial dysfunction, characterized by decreased bioavailability of NO, is a predictor of cardiovascular risk and outcome (24)(25)(26)(27)(28).…”

Endothelin ET A receptor blockade restores NO-mediated endothelial function and inhibits atherosclerosis in apolipoprotein E-deficient mice

“…In patients with cardiovascular risk factors such as hypercholesterolemia, hypertension, or aging (2,3), endothelial dysfunction precedes the development of atherosclerosis and predisposes to the development of structural vascular changes (1,4). The endothelium releases vasoactive mediators such as NO and endothelin (ET-1), both of which are importantly involved in the regulation of vascular tone (5,6) and structure (7,8).…”