Increased vascular reactive oxygen species production, especially superoxide anion, contributes significantly in the functional and structural alterations present in hypertension. An enhanced superoxide production causes a diminished NO bioavailability by an oxidative reaction that inactivates NO. Exaggerated superoxide levels and a low NO bioavailability lead to endothelial dysfunction and hypertrophy of vascular cells. It has been shown that the enzyme NAD(P)H oxidase plays a major role as the most important source of superoxide anion in vascular cells. Several experimental observations have shown an enhanced superoxide generation as a result of the activation of vascular NAD(P)H oxidase in hypertension. Although this enzyme responds to stimuli such as vasoactive factors, growth factors, and cytokines, some recent data suggest the existence of a genetic background modulating the expression of its different components. New polymorphisms have been identified in the promoter of the p22
phox
gene, an essential subunit of NAD(P)H oxidase, influencing the activity of this enzyme. Genetic investigations of these polymorphisms will provide novel markers for determination of genetic susceptibility to oxidative stress in hypertension.
Myocardial fibrosis impairs cardiac function, in addition to facilitating arrhythmias and ischemia, and thus influences the evolution and outcome of cardiac diseases. Its assessment is therefore clinically relevant. Although tissue biopsy is the gold standard for the diagnosis of myocardial fibrosis, a number of circulating biomarkers have been proposed for the noninvasive assessment of this lesion. A review of the published clinical data available on these biomarkers shows that most of them lack proof that they actually reflect the myocardial accumulation of fibrous tissue. In this "call to action" article, we propose that this absence of proof may lead to misinterpretations when considering the incremental value provided by the biomarkers with respect to traditional diagnostic tools in the clinical handling of patients. We thus argue that strategies are needed to more strictly validate whether a given circulating biomarker actually reflects histologically proven myocardial fibrosis before it is applied clinically.
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