Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery

Abstract

eNOS transduction in atherosclerotic human carotid artery results in high expression without any measurable activity of the recombinant protein. The defect in the atherosclerotic vessels is neither caused by cofactor deficiency nor enhanced NO breakdown. Since angioplasty is performed in atherosclerotic arteries,eNOS gene therapy is unlikely to provide clinical benefit.

Direct relationship between levels of TNF-α expression and endothelial dysfunction in reperfusion injury

“…Endothelial dysfunction appears to occur early after reperfusion, signaled by the endothelial generation of a large burst of superoxide radicals [8, 11, 20, 28, 29, 31, 36]. The decrease in endothelium-dependent dilation has been shown to occur soon after the generation of O 2 ·− by the reperfused coronary endothelium [20, 31] suggesting that endothelial generation of O 2 ·− radicals acts as a trigger mechanism for endothelial dysfunction.…”

Vascular control in humans: focus on the coronary microcirculation

“…In addition, other studies also reported that release of TNF- α during stent implantation also contributes to impaired dilator response in coronary microcirculation [12]. Many other factors, such as endothelial progenitor cells [38], substances released from surrounding myocardium [53], alteration of NOS gene [139], and endothelial growth factor [62], have also been reported to regulate coronary vasomotor tone.…”

Angiotensin II impairs endothelial function via tyrosine phosphorylation of the endothelial nitric oxide synthase

“…Correspondingly, eNOS gene transfer is considered an attractive therapeutic option to improve endothelial function. However, although the exogenous expression of eNOS successfully prevented smooth muscle cell migration in vitro (Largiadèr et al, 2008), a similar approach in human atherosclerotic lesions failed because the heterologously expressed eNOS was inactive (Tanner et al, 2007). eNOS.…”