Endothelial dysfunction : the early predictor of atherosclerosis

Abstract

Since the discovery in the 1980s that nitric oxide (NO) is in fact the elusive endothelium-derived relaxing factor, it has become evident that NO is not only a major cardiovascular signalling molecule, but that changes in its bioavailability are crucial in determining whether atherosclerosis will develop or not. Sustained high levels of harmful circulating stimuli associated with cardiovascular risk factors such as diabetes mellitus elicit responses in endothelial cells that appear sequentially, namely endothelial cell activation and endothelial dysfunction (ED).ED, characterised by reduced NO bioavailability, is now recognised by many as an early, reversible precursor of atherosclerosis. The pathogenesis of ED is multifactorial; however, oxidative stress appears to be the common underlying cellular mechanism in the ensuing loss of vaso-active, inflammatory, haemostatic and redox homeostasis in the body’s vascular system. The role of ED as a pathophysiological link between early endothelial cell changes associated with cardiovascular risk factors and the development of ischaemic heart disease is of importance to basic scientists and clinicians alike.

Eicosapentaenoic Acid Prevents Saturated Fatty Acid-Induced Vascular Endothelial Dysfunction: Involvement of Long-Chain Acyl-CoA Synthetase

“…When vascular endothelial cells are damaged, monocyte migration, the release of adhesion molecules, inflammatory cytokines, coagulation factors, etc., and macrophage infiltration into tissues are initiated, which leads to the promotion of atherosclerosis development and progression 13) . It is known that saturated fatty acids initiate inflammatory signaling and oxidative stress in vascular endothelial cells.…”

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

“…1). Beyond vascular homeostasis and vascular tone, it orchestrates diverse functions: smooth muscle cell proliferation [3,4], transendothelial leukocyte diapedesis [5,6], and thrombosis and thrombolysis [7].…”

Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium

“…In addition, the interaction of AGEs with their receptor (RAGE) on the cell surface causes upregulation of transcription factors such as nuclear factor (NF)-jB, leading to the expression of various pro-inflammatory cytokines and cell adhesion molecules that cause increased recruitment of monocytes into endothelial cells (ECs). This implies that AGEs-RAGE interactions are key steps in EC dysfunction and atherosclerosis (Davignon & Ganz 2004;Sitia et al 2010;Mudau et al 2012). In the pathogenesis of vessel disease, the proliferation of vascular smooth muscle cells (VSMCs) is an important event in the progression and rupture of atherosclerotic plaque, which subsequently contributes to heart disease (Ross 1993).…”