Genetic abnormalities of the endothelium

Abstract

Endothelial cell dysfunction plays an important role in the development and progression of cardiovascular and other disease. The purpose of this review is to discuss some of the genetic diseases known to adversely affect endothelial function. Although the list is exhaustive, we focus our discussion on primary pulmonary hypertension, diabetes mellitus, Alzheimer's disease, Crohn's disease, Von-Hippel-Lindau disease, familial Mediterranean fever, thrombotic microangiopathy, and key vascular malformations. Endothelial dysfunction results from a complex interplay between genetic and environmental factors. This review highlights some of the growing body of evidence implicating endothelial dysfunction as an important mediator of diverse diseases.

Endothelium and Its Alterations in Cardiovascular Diseases: Life Style Intervention

“…First isolated, purified, and sequenced in 1988 [41], in health, the production of ET-1 is minimal and it is effectively opposed by NO and other endothelium derived vasodilators [42]. The circulating level of this short peptide was quickly determinant in humans and it was reported that, in most cardiovascular diseases, circulating level of ET-1 was increased [43].…”

“…Endothelial dysfunction is known to be implicated in the pathogenesis and clinical course of all known cardiovascular diseases [136, 137], occurs in response to cardiovascular risk factors, and precedes the development of atherosclerosis [42, 138, 139]. Endothelial dysfunction actively participates in the process of lesion formation promoting the early and late mechanisms of atherosclerosis [32, 40, 42], determining increase in EC permeability, upregulation of adhesion molecules, chemokine and cytokine secretion, and leukocyte adherence, enhanced oxidized-low density lipoprotein (ox-LDL), platelet activation, and vascular smooth muscle cell proliferation and migration.…”

“…Endothelial dysfunction actively participates in the process of lesion formation promoting the early and late mechanisms of atherosclerosis [32, 40, 42], determining increase in EC permeability, upregulation of adhesion molecules, chemokine and cytokine secretion, and leukocyte adherence, enhanced oxidized-low density lipoprotein (ox-LDL), platelet activation, and vascular smooth muscle cell proliferation and migration. In addition, endothelial dysfunction is not only the initial stage of the development of atherosclerotic disease that generates plaque formation, but it also can cause plaque growth leading to vascular complications.…”

“…There are also evidences to suggest that abnormalities of endothelium-dependent vasodilatation contribute to the clinical syndromes of microvascular angina and coronary vasospasm [42]. …”

Nitrates and Nitrites in the Treatment of Ischemic Cardiac Disease

“…When the endothelium deteriorates or becomes dysfunctional, blood flow is disturbed and vessels become obstructed, leading to ischemia of downstream organs including the heart [66–71]. Endothelial damage is associated with most forms of CVD, including hypertension, coronary artery disease, CHF, peripheral artery disease, diabetes, chronic renal failure, and pulmonary hypertension [72–76]. Endothelial function is altered in the presence of cardiovascular risk factors, suggesting that endothelial dysfunction is likely to be an important first step in CVD [77–86].…”