Role of Oxidative Stress in Heart Failure: Insights from Gene Transfer Studies

Abstract

Under physiological circumstances, there is an exquisite balance between reactive oxygen species (ROS) production and ROS degradation, resulting in low steady-state ROS levels. ROS participate in normal cellular function and in cellular homeostasis. Oxidative stress is the state of a transient or a persistent increase of steady-state ROS levels leading to disturbed signaling pathways and oxidative modification of cellular constituents. It is a key pathophysiological player in pathological hypertrophy, pathological remodeling, and the development and progression of heart failure. The heart is the metabolically most active organ and is characterized by the highest content of mitochondria of any tissue. Mitochondria are the main source of ROS in the myocardium. The causal role of oxidative stress in heart failure is highlighted by gene transfer studies of three primary antioxidant enzymes, thioredoxin, and heme oxygenase-1, and is further supported by gene therapy studies directed at correcting oxidative stress linked to metabolic risk factors. Moreover, gene transfer studies have demonstrated that redox-sensitive microRNAs constitute potential therapeutic targets for the treatment of heart failure. In conclusion, gene therapy studies have provided strong corroborative evidence for a key role of oxidative stress in pathological remodeling and in the development of heart failure.

Berberine Alleviates Doxorubicin-Induced Myocardial Injury and Fibrosis by Eliminating Oxidative Stress and Mitochondrial Damage via Promoting Nrf-2 Pathway Activation

“…Several studies have reported that DOX tends to induce the generation of ROS during metabolism [ 50 , 51 ]. Compared with other tissues, the myocardium is more vulnerable to oxidative stress, possibly due to low levels of antioxidant enzymes that scavenge ROS [ 52 , 53 ]. Consistent with previous studies, our results confirmed that DOX promoted ROS production in the myocardium of rats.…”

Research status and trends of the diabetic cardiomyopathy in the past 10 years (2012–2021): A bibliometric analysis

“…The top three keywords in frequency in the past decade are apoptosis (216 times), oxidative stress (213 times), and fibrosis (192 times), respectively ( Figure 9 ). Diabetes is characterized by oxidative stress and low-grade inflammation ( 59 ). Under physiological circumstances, a delicate balance between the production and degradation of ROS resulting an average steady-state ROS level.…”

Increased Remnant Lipoproteins in Apo E Deficient Mice Induce Coronary Atherosclerosis following Transverse Aortic Constriction and Aggravate the Development of Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

“…Hypercholesterolemia also potentiates cardiac hypertrophy and adverse remodeling following myocardial infarction [ 31 , 62 ] and in the setting of diabetic cardiomyopathy [ 63 ]. Oxidative stress and nitro-oxidative stress may play a key role in the effects of hypercholesterolemia on cardiac structure and function [ 64 , 65 , 66 ]. Hypercholesterolemia also induces hyperactive mammalian target of rapamycin (mTOR) signaling in the heart, whereby protein synthesis and cell growth are promoted by the mTOR complex 1 (mTORC1) [ 22 , 67 , 68 ].…”

“…This may clarify why oxidative stress was elevated in apo E deficient mice even in the absence of TAC. Since inflammation [ 72 ] and oxidation [ 66 ] contribute to the development of heart failure, this may explain why apo E deficiency per se may be a potent potentiator of pressure-induced heart failure. Increased oxidative stress may also underlie diastolic dysfunction in C57BL/6N apo E −/− sham mice [ 73 ].…”