Key Mechanisms of Oxidative Stress-Induced Ferroptosis in Heart Failure with Preserved Ejection Fraction and Potential Therapeutic Approaches.

Abstract

The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing annually, particularly among patients with metabolic disorders such as hypertension and diabetes. However, there is currently no treatment capable of altering the natural course of HFpEF. Recently, the interplay between oxidative stress and ferroptosis in cardiovascular diseases has drawn extensive attention; however, minimal research has been published on the mechanisms of oxidative stress and ferroptosis in HFpEF. This paper reviews the relevant mechanisms through which oxidative stress is induced and promotes ferroptosis during the development of HFpEF. The review also explores more efficacious treatment approaches for HFpEF by inhibiting oxidative stress and ferroptosis, thereby offering a theoretical foundation for verifying the feasibility of these methods for further research. As tumor-targeted therapy progresses, the survival period of tumor patients is prolonged, and cardiovascular events have gradually emerged as one of the most crucial causes of death among tumor patients. Hence, inhibiting the vascular endothelial growth factor (VEGF) pathway has become a major target in tumor treatment, significantly enhancing patient survival. Nevertheless, secondary cardiovascular complications and events, such as myocardial injury and subsequent heart failure, have severely impacted patient survival and quality of life. Therefore we have also explored the potential mechanism through which novel targeted anti-cancer drugs induce HFpEF via ferroptosis. Additionally, we reviewed the specific modes of action for preventing and treating HFpEF without influencing their anti-cancer therapeutic effect.