Pathomechanism of oxidative stress in cardiovascularrenal remodeling and therapeutic strategies

Abstract

The high prevalence of cardiovascular disease in patients with chronic kidney disease indicates significant interactions between pathogenic pathways operating in the kidney and heart. These interactions involve all cell types (endothelial cells, smooth muscle cells, macrophages, and others), components of the vasculature, glomeruli, and heart that are susceptible to oxidative damage and structural alterations. A vicious cycle occurs whereby harmful factors such as reactive oxygen species and inflammation damage of vascular structures that themselves become sources of additional dangerous/toxic components released into the local environment. The evidence of this vicious cycle in chronic kidney disease should therefore lead to add other factors to both traditional and nontraditional risk factors. This review will examine the processes occurring during progressive kidney dysfunction with regard to vascular injury, renal remodeling, cardiac hypertrophy, and the transversal role of oxidative stress in the development of these complications.

The RAAS Goodfellas in Cardiovascular System

“…Several studies from our group reported a strong activation of the ACE2/Ang 1-7/MasR axis in BS/GS patients, coupled with a reduced expression of proteins involved in the oxidative stress (as p22 phox ), reduced activation of the RhoA/Rho-kinase pathways, increase NO production and endothelial protection [15,18,19,78]. A comparative study between normotensive, hypertensive, and BS/GS patients reported that the p63RhoGEF, both at mRNA and protein level and MYPT-1 phosphorylation status were higher in hypertensive patients and lower in BS/GS patients compared to controls [79] (Figure 2).…”

Sarcopenia in chronic kidney disease: from bench to bedside

“…Oxidative stress and inflammation are features of CKD [155] and they also induce muscle wasting. Through the nuclear factor kappa-light-chain-enhancer of activated B cells pathway, reactive oxygen species (ROS)-induced tumor necrosis factor (TNF)-α activates myostatin expression [137] and increased inflammatory cytokines, such as TNF-α and interleukin (IL)-6, causing muscle atrophy in patients with CKD [156][157][158].…”

Oxidants and Cardiorenal Vascular Remodeling—Insights from Rare Genetic Tubulopathies: Bartter’s and Gitelman’s Syndromes

“…There are multiple mechanisms through which ROS can potentially stimulate AF, by causing increased ion leak throughout mycardiocytes [ 26 ], as well as by stimulating collagen deposition and fibrosis that interferes with the propagation of the electric impulse [ 29 ]. Ang II increases Rho kinase (ROCK) activity, leading to elevated myosin phosphatase target protein subunit-1 (MYPT-1) phosphorylation, and to the increased expression of Connexin 40, an integral membrane protein of heart gap cells junction, which enhances atrial vulnerability to electrical disturbances [ 30 , 31 ].…”