Oxidative Stress-Induced Ferroptosis in Cardiovascular Diseases and Epigenetic Mechanisms

Abstract

The recently discovered ferroptosis is a new kind of iron-regulated cell death that differs from apoptosis and necrosis. Ferroptosis can be induced by an oxidative stress response, a crucial pathological process implicated in cardiovascular diseases (CVDs). Accordingly, mounting evidence shows that oxidative stress-induced ferroptosis plays a pivotal role in angio-cardiopathy. To date, the inhibitors and activators of ferroptosis, as well as the many involved signaling pathways, have been widely explored. Among which, epigenetic regulators, molecules that modify the package of DNA without altering the genome, emerge as a highly targeted, effective option to modify the signaling pathway of ferroptosis and oxidative stress, representing a novel and promising therapeutic potential target for CVDs. In this review, we will briefly summarize the mechanisms of ferroptosis, as well as the role that ferroptosis plays in various CVDs. We will also expound the epigenetic regulators of oxidative stress-induced ferroptosis, and the promise that these molecules hold for treating the intractable CVDs.

Exploration of ferroptosis-related genes and molecular mechanisms in psoriasis and atherosclerosis

“…Inhibiting STAT3 phosphorylation was able to reduce the expression of pro-in ammatory mediators in the serum and skin lesions of PsD mice, according to a different study that found STAT3 to be signi cantly elevated in lesional skin in a PsD mouse model [31]. SIRT1, the most widely studied member of the SIRT family in mammals, is able to reduce in ammation and oxidative stress by inhibiting mitochondrial ROS production and reducing hydrogen peroxide levels at the cardiovascular level, as well as reducing iron death in foam cells by activating autophagy, thus providing a new therapeutic [32] target for AS [33]. Additionally, it has been reported that activation of the SIRT1 signaling pathway in broblasts from PsD patients shows a bene cial role in restoring mitochondrial function and redox homeostasis by controlling MAPK signaling; as a result, SIRT1 may represent a novel molecular target for the treatment of PsD.…”

Extracellular histone H3 facilitates ferroptosis in sepsis through ROS/JNK pathway

“…Notably, the ratio of GSH/GSSG is a maker for evaluating the redox state of the cell or tissue 29 . Oxidative stress is also a well‐studied inducer of ferroptosis, an iron‐dependent of nonapoptotic cell death 30 . Moreover, Gpx4 is capable of limiting ferroptosis under normal conditions, and its downregulation during oxidative stress can induce cell death 7 .…”

Sesamin attenuates PM2.5-induced cardiovascular injury by inhibiting ferroptosis in rats

“…16 In fact, iron deposition and lipid peroxidation, the major features of ferroptosis, are strongly associated with inflammatory response and oxidative stress. 41,42 Glutathione acts as an important antioxidant and a free radical scavenger in vivo and it can be categorized as either reduced (GSH) or oxidized (GSSG). GPx4 converts GSH into GSSG and GSH/GSSG constitutes an antioxidant system that provides reducing equivalents to eliminate oxidative species.…”

“…GPx4 converts GSH into GSSG and GSH/GSSG constitutes an antioxidant system that provides reducing equivalents to eliminate oxidative species. 41,43 Cellular iron overload can lead to mitochondrial dysfunction and increased ROS production that even exceeds the scavenging capacity of antioxidant systems ( e.g. , GSH and GPX4), thereby forming lipid peroxides, enhancing oxidative stress, and promoting the release of pro-inflammatory mediators.…”

“…, GSH and GPX4), thereby forming lipid peroxides, enhancing oxidative stress, and promoting the release of pro-inflammatory mediators. 41,42 A recent review highlighted that ferroptosis may be the initiating factor for inflammation or at least has proinflammatory effects. 42 These findings suggest that ferroptosis may play a major role in the occurrence and development of CVDs.…”