Oxidative Stress and Autophagy in Cardiovascular Homeostasis

Abstract

Significance: Autophagy is an evolutionarily ancient process of intracellular protein and organelle recycling required to maintain cellular homeostasis in the face of a wide variety of stresses. Dysregulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to oxidative damage. Both autophagy and ROS/RNS serve pathological or adaptive roles within cardiomyocytes, depending on the context. Recent Advances: ROS/RNS and autophagy communicate with each other via both transcriptional and post-translational events. This cross talk, in turn, regulates the structural integrity of cardiomyocytes, promotes proteostasis, and reduces inflammation, events critical to disease pathogenesis. Critical Issues: Dysregulation of either autophagy or redox state has been implicated in many cardiovascular diseases. Cardiomyocytes are rich in mitochondria, which make them particularly sensitive to oxidative damage. Maintenance of mitochondrial homeostasis and elimination of defective mitochondria are each critical to the maintenance of redox homeostasis. Future Directions: The complex interplay between autophagy and oxidative stress underlies a wide range of physiological and pathological events and its elucidation holds promise of potential clinical applicability. Antioxid. Redox Signal. 20, 507-518.

Spliced XBP1 promotes macrophage survival and autophagy by interacting with Beclin-1

“…Atherosclerosis is a multistep process that involves many factors, such as platelet aggregation [23], hypertension [24]. In recent years, researchers have become interested in autophagy, which can be triggered by oxidative stress [11] or hypoxia [12]. However, the factors that can induce autophagy are still unclear.…”

“…However, the regulation of macrophage autophagy in atherosclerotic plaques needs to be fully elucidated. Autophagy is a multistep catabolic process that has been shown to be involved in a variety of pathophysiological conditions such as oxidative stress [6,11], hypoxia [12], ischemia-reperfusion [13]. During the process of autophagy, long-lived proteins and organelles are sequestered into a double membrane-bound autophagosome and degraded by a lysosome [14].…”

Vitamin D Receptor Activation Protects Against Myocardial Reperfusion Injury Through Inhibition of Apoptosis and Modulation of Autophagy

“…This study provided a novel cardioprotective mechanism for VDR by decrease of autophagy dysfunctionmediated cell death in the setting of MI/R. Oxidative stress has been recognized as a major mediator of MI/R injury, and is causatively related to ER stress, mitochondrial impairment, and autophagy dysfunction (19,24,39,48). Thus, we further examined the effects of VDR activation on oxidative stress.…”

“…Early reperfusion is the best strategy for the rescue of ischemic myocardium. However, myocardial reperfusion leads to the excessive production of reactive oxygen species (ROS)/reactive nitrogen species, the activation of apoptotic pathways, and the induction of autophagy dysfunction, all of which contribute to postischemic cardiomyocyte death and exacerbate myocardial injury (20,39,40). Novel pharmacological or molecular interventions mitigating reperfusion injury, adjunctive to current reperfusion therapies, are in great need (22).…”

The role of mitochondria in cardiac development and protection

“…Hypoxia and oxidative damage have been shown to induce autophagy in cardiomyocytes [33] and are induced via the mitochondrially regulated AMPK-ULK1 signaling pathway [23]. Interestingly, autophagy seems to have a protective role in mild ischemia but can develop to be detrimental after ischemia-reperfusion [43,44]. The latter could result from the overload of autophagosome processing as well as delayed clearance of damaged organelles, resulting in increased ROS generation and cell death following MPTP opening.…”