Key result
Endothelial dysfunction predicts coronary artery disease risk, driven by impaired nitric oxide bioavailability.
Highlights the central role of nitric oxide-mediated endothelial function in coronary blood flow regulation and its impairment as a primary driver of coronary artery disease.
Endothelial dysfunction assessment may refine CAD risk stratification; leaves open whether targeting nitric oxide pathways improves outcomes in trials.
Nitric oxide (NO) formed via endothelial NO synthase (eNOS) plays crucial roles in the regulation of coronary blood flow through vasodilatation and decreased vascular resistance, and in inhibition of platelet aggregation and adhesion, leading to the prevention of coronary circulatory failure, thrombosis, and atherosclerosis. Endothelial function is impaired by several pathogenic factors including smoking, chronic alcohol intake, hypercholesterolemia, obesity, hyperglycemia, and hypertension. The mechanisms underlying endothelial dysfunction include reduced NO synthase (NOS) expression and activity, decreased NO bioavailability, and increased production of oxygen radicals and endogenous NOS inhibitors. Atrial fibrillation appears to be a risk factor for endothelial dysfunction. Endothelial dysfunction is an important predictor of coronary artery disease (CAD) in humans. Penile erectile dysfunction, associated with impaired bioavailability of NO produced by eNOS and neuronal NOS, is also considered to be highly predictive of ischemic heart disease. There is evidence suggesting an important role of nitrergic innervation in coronary blood flow regulation. Prophylactic and therapeutic measures to eliminate pathogenic factors inducing endothelial and nitrergic nerve dysfunction would be quite important in preventing the genesis and development of CAD.
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Toda et al. (2011) conducted a review in Coronary Artery Disease. Nitric oxide was evaluated. Endothelial dysfunction, driven by reduced nitric oxide bioavailability and increased endogenous inhibitors like asymmetric dimethylarginine, acts as an important predictor and pathogenic factor for coronary artery disease.
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