Intersection of the Ubiquitin–Proteasome System with Oxidative Stress in Cardiovascular Disease

Abstract

Cardiovascular diseases (CVDs) present a major social problem worldwide due to their high incidence and mortality rate. Many pathophysiological mechanisms are involved in CVDs, and oxidative stress plays a vital mediating role in most of these mechanisms. The ubiquitin–proteasome system (UPS) is the main machinery responsible for degrading cytosolic proteins in the repair system, which interacts with the mechanisms regulating endoplasmic reticulum homeostasis. Recent evidence also points to the role of UPS dysfunction in the development of CVDs. The UPS has been associated with oxidative stress and regulates reduction–oxidation homeostasis. However, the mechanisms underlying UPS-mediated oxidative stress’s contribution to CVDs are unclear, especially the role of these interactions at different disease stages. This review highlights the recent research progress on the roles of the UPS and oxidative stress, individually and in combination, in CVDs, focusing on the pathophysiology of key CVDs, including atherosclerosis, ischemia–reperfusion injury, cardiomyopathy, and heart failure. This synthesis provides new insight for continued research on the UPS–oxidative stress interaction, in turn suggesting novel targets for the treatment and prevention of CVDs.

Integrative chemoproteomics reveals anticancer mechanisms of silver(i) targeting the proteasome regulatory complex

“…4 ), both of which are located in the ubiquitin receptor domain and are responsible for recruiting ubiquitinated proteins for degradation. Previous studies reported that proteasome activity can be regulated through oxidation of proteasome subunits, 66 and therefore oxidation of the ADRM1 cysteine may interfere with the degradation process. However, overall proteasome oxidation levels ranged from 49% to 74%, indicating that AgTU treatment induced mild oxidation.…”

Proliferation, migration and phenotypic transformation of VSMC induced via Hcy related to up-expression of WWP2 and p-STAT3

“…WWP2, encoded by the WWP2 gene, is expressed in several tissues/organs throughout the human body and regulates several cellular, physiological and pathological processes [ 29 , 30 ]. WWP2 was associated with oxidative stress-mediated VSMC injury in different cardiovascular diseases, such as AS, ischemia-reperfusion injury, cardiomyopathy and heart failure [ 31 , 32 ], suggested that WWP2 could be a significant target for treating several cardiovascular diseases.…”

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