Molecular mechanisms of iron metabolism and ferroptosis in cardiovascular diseases and intervention strategies targeting natural products (Review).

Abstract

Obesity, hypertension and high cholesterol diets are factors that contribute to the development of cardiovascular diseases (CVDs), posing risks to both physical and mental health. The occurrence and progression of CVDs are associated with multiple cell death pathways, such as ferroptosis and autophagy. Ferroptosis, a relatively recently identified form of regulated cell death, is an iron‑dependent process of lipid peroxidation that can accumulate to lethal levels, resulting in oxidative damage to cell membranes. The mechanism of ferroptosis involves glutathione (GSH) depletion, iron overload and excessive production of reactive oxygen species (ROS). Iron homeostasis plays a crucial role in maintaining cardiac function and is closely related to the occurrence and progression of CVDs. Studies of various CVD models have found that the major metabolic pathways regulating ferroptosis include iron metabolism, GSH metabolism and lipid metabolism. Modulating these metabolic pathways can regulate the occurrence and execution of ferroptosis in cardiac myocytes, potentially improving CVDs. Targeting the metabolic pathways of ferroptosis may become a new therapeutic direction for CVDs. Therefore, the present review summarized the relationship between ferroptosis and various CVDs, including myocardial diseases, heart failure, atherosclerosis, myocardial ischemia, reperfusion injury, hypertension and aortic dissection, to offer new insights into CVD treatment. In addition, it summarized the inhibitors targeting ferroptosis in CVDs, such as iron chelators (deferoxamine and deferiprone), ROS inhibitors, lipid peroxidation inhibitors and antioxidants (such as alpha‑lipoic acid, selenium), which have been proven to be effective in basic experiments and clinical trials and can exert cardiovascular protection.