Atherosclerosis, Coronary Artery Disease and Endothelium
One of the foremost leaders of mortality in the US is coronary artery disease (CAD). This disease strikes many older men and women, as a result from the infamous factors of high cholesterol, high blood pressure, and diabetes mellitus, not to mention others. Thanks to research over the last decade, there is more understanding of the role endothelium plays in the coronary system. Instead of having non-active, diffusional barrier-like qualities, as was once thought, the endothelium serves many critically important functions. At the blood vessel walls, the endothelium synthesizes and releases active substances such as nitric oxide and bradykinin, two potent regulators of vessel function. It is found that the physiologic changes in the endothelium affect the mechanisms responsible for atherosclerosis, and progressively in coronary artery disease. The changes that generate these conditions are known as endothelial dysfunction. As we will see, even the smallest factors can play a widespread role in atherogenesis, or the making of degenerative plaques of cholesterol in the inner layer of an artery. Atherosclerosis, a condition increasing with age, is marked by the deposition of lipids into already-present plaques, causing elevate
PAI-1 is selected for by the conversion of angiotensin II into angiotensin IV. Also important to note is that while nitric oxide and all vasoconstrictors have the opposing effects, releasing excess amounts of vasoconstrictors is not shown to reduce the degree of effect of nitric oxide (Pepine et al, 1997). To function, nitric oxide production is stimulated by receptors on the endothelium responding to physical stimuli, such as shear stress, or physiologic stimuli such as bradykinin and acetylcholine. Smoking leads to dysfunction since nicotine is proposed to enhance platelet-vessel wall binding, reduce prostacyclin, increase circulating and endogenous low-density lipoproteins, and increase oxidation by superoxide anion (Pepine et al, 1997). The endothelium produces L-arginine, and this is converted by nitric oxide synthase into nitric oxide. Finally, genetic predisposition increases risk due to the level of gene protein homocysteine. Different factors will tamper with this regular function, and are explained later. The nitric oxide released into the lumen binds to cGMP, and concentration of cGMP increases, to inhibit smooth muscle cell proliferation. Bradykinin has important inhibitory qualities including he release of nitric oxide, by acting on endogenous receptors that activate the L-arginine to nitric oxide reaction. Nitric oxide travels into the smooth muscle cells, where it elevates the level of cyclic GMP, which relaxes the muscle. Another inhibitor of platelet aggregation is when endothelial cells convert platelet-derived endoperoxidases to prostacyclin (Pepine et al, 1997). Prostacyclin is transported into the smooth muscle cell and raises the level of cyclic AMP to relax the cell, while endothelium-derived hyperpolarizing factor opens more potassium channels in the smooth muscle cell membrane (Pepine et al, 1997). These are circulating nitric oxide, cyclic GMP, and L-arginine, a precursor of nitric oxide. This protein acts on a receptor that may express PAI-1, and PAI-1 may in turn lead to thrombosis (Pepine et al, 1997). There are a multitude of factors established that are highly related to endothelial dysfunction.
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Acceptance Essays
