Abstract
Vascular inflammation in atheroprone vessels propagates throughout the arterial tree in dyslipidemic patients, thereby accelerating atherosclerotic progression. To elucidate the mechanism of vascular inflammation, most previous studies have focused on inflammation-related signals that are sent in response to vasoactive stimuli. However, it is also important to understand how normal blood vessels become defective and start degenerating. Growing evidence suggests that major protein catabolism pathways, including the ubiquitin-proteasome, autophagy, and calpain systems, are disturbed in atheroprone vessels and contribute to the pathogenesis of atherosclerosis. Indeed, dysregulation of ubiquitin–proteasome pathways results in the accumulation of defective proteins in blood vessels, leading to vascular endothelial dysfunction and apoptosis in affected cells. Impaired autophagy-lysosomal degradation affects smooth muscle cell transformation and proliferation, as well as endothelial integrity and phagocytic clearance of cellular corpses. Dysregulation of the calpain system confers proatherogenic properties to endothelial cells, smooth muscle cells, and macrophages. In this review article, we will discuss the current information available on defective protein catabolism in atheroprone vessels and its potential interrelation with inflammation-related signals.
Highlights
Atherosclerosis is a chronic inflammatory disease accompanied by the intimal thickening of systemic arterial walls [1, 2]
Regarding the pathogenic cues that contribute to atherosclerosis, the majority of previous atherosclerosis studies support the hypothesis that atherosclerosis is driven through reactive oxygen species (ROS)-mediated oxidative stress, which leads to the induction of numerous inflammatory elements, such as adhesion molecules in vascular endothelial cells (ECs) and proinflammatory cytokines via redox-sensitive transcription factors [2]
Earlier clinical trials investigated the efficacy of antioxidants, these agents failed to reverse cardiovascular death [4]; in contrast, they were effective in ameliorating acute inflammation, including the acute phase of Protein Catabolism and Atherosclerosis stroke [5]
Summary
Specialty section: This article was submitted to Atherosclerosis and Vascular Medicine, a section of the journal Frontiers in Cardiovascular Medicine. Defective Protein Catabolism in Atherosclerotic Vascular Inflammation. Vascular inflammation in atheroprone vessels propagates throughout the arterial tree in dyslipidemic patients, thereby accelerating atherosclerotic progression. Growing evidence suggests that major protein catabolism pathways, including the ubiquitin-proteasome, autophagy, and calpain systems, are disturbed in atheroprone vessels and contribute to the pathogenesis of atherosclerosis. Dysregulation of ubiquitin–proteasome pathways results in the accumulation of defective proteins in blood vessels, leading to vascular endothelial dysfunction and apoptosis in affected cells. Impaired autophagy-lysosomal degradation affects smooth muscle cell transformation and proliferation, as well as endothelial integrity and phagocytic clearance of cellular corpses. Dysregulation of the calpain system confers proatherogenic properties to endothelial cells, smooth muscle cells, and macrophages. We will discuss the current information available on defective protein catabolism in atheroprone vessels and its potential interrelation with inflammation-related signals
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