Isopropyl 3-(3,4-Dihydroxyphenyl)-2-hydroxypropanoate Alleviates Palmitic Acid-Induced Vascular Aging in HUVEC Cells through ROS/Ferroptosis Pathway

Abstract

Vascular aging is an important factor leading to cardiovascular diseases such as hypertension and atherosclerosis. Hyperlipidemia or fat accumulation may play an important role in vascular aging and cardiovascular disease. Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) has biological activity and can exert cardiovascular protection, which may be related to ferroptosis. However, the exact mechanism remains undefined. We hypothesized that IDHP may have a protective effect on blood vessels by regulating vascular aging caused by hyperlipidemia or vascular wall fat accumulation. The aim of this study is to investigate the protective effect and mechanism of IDHP on palmitic acid-induced human umbilical vein endothelial cells (HUVEC) based on senescence and ferroptosis. We found that IDHP could delay vascular aging, reduce the degree of ferrous ion accumulation and lipid peroxidation, and protect vascular cells from injury. These effects may be achieved by attenuating excessive reactive oxygen species (ROS) and ferroptosis signaling pathways generated in vascular endothelial cells. In short, our study identified IDHP as one of the antioxidant agents to slow down lipotoxicity-induced vascular senescence through the ROS/ferroptosis pathway. IDHP has new medicinal value and provides a new therapeutic idea for delaying vascular aging in patients with dyslipidemia.