Noncoding RNAs regulating ferroptosis in cardiovascular diseases: novel roles and therapeutic strategies

Abstract

The morbidity and mortality rates of cardiovascular diseases (CVDs) are increasing; thus, they impose substantial health and economic burdens worldwide, and effective interventions are needed for immediate resolution of this issue. Recent studies have suggested that noncoding RNAs (ncRNAs) play critical roles in the occurrence and development of CVDs and are potential therapeutic targets and novel biomarkers for these diseases. Newly discovered modes of cell death, including necroptosis, pyroptosis, apoptosis, autophagy-dependent cell death and ferroptosis, also play key roles in CVD progression. However, ferroptosis, which differs from the other aforementioned forms of regulated cell death in terms of cell morphology, biochemistry and inhereditability, is a unique iron-dependent mode of nonapoptotic cell death induced by abnormal iron metabolism and excessive accumulation of iron-dependent lipid peroxides and reactive oxygen species (ROS). Increasing evidence has confirmed that ncRNA-mediated ferroptosis is involved in regulating tissue homeostasis and CVD-related pathophysiological conditions, such as cardiac ischemia/reperfusion (I/R) injury, myocardial infarction (MI), atrial fibrillation (AF), cardiomyopathy and heart failure (HF). In this review, we summarize the underlying mechanism of ferroptosis, discuss the pathophysiological effects of ncRNA-mediated ferroptosis in CVDs and provide ideas for effective therapeutic strategies.

Keywords: Cardiovascular diseases; Ferroptosis; Iron metabolism; Lipid peroxidation; Molecular mechanism; Noncoding RNA.

Fig. 1

Molecular signaling mechanisms and pathways involved in ferroptosis. Different physiological processes and pathological stresses may trigger ferroptosis. Abnormal iron metabolism, excess ROS production and excessive accumulation of lipid peroxide are important factors that induce ferroptosis. Abbreviations: DcytB: duodenal cytochrome B reductase; EPO: erythropoietin; GSSG: glutathione disulfide; iFSP: inhibitor of FSP1; L-OOH: lipid peroxide; L-OH: lipid alcohol; and NADPH: nicotinamide adenine dinucleotide phosphate