Abstract
Objective To investigate the protective effects and regulatory mechanisms of ferulic acid on oxidative stress-induced cardiomyocyte injury. Methods We established a cardiomyocyte oxidative stress cell model by H2O2 treatment and a mouse heart injury model by isoprenaline infusion of male C57BL/6 mice. Ferulic acid was applied to treat oxidative stress-induced cardiomyocyte injury. DHE staining was used to detect ROS production. DNA fragmentation, TUNEL assay, and cleaved caspase-3 were used to analyze cell apoptosis. Real-time PCR and Western blotting were used to analyze miRNA and protein levels to investigate the regulatory mechanisms of ferulic acid on oxidative stress-induced cardiomyocyte injury. Results Ferulic acid pretreatment significantly inhibited H2O2- and isoprenaline-induced oxidative stress and cell apoptosis by promoting miR-499-5p expression and inhibiting p21 expression. MiR-499-5p inhibition reversed the protective effects of ferulic acid. Further study found that ferulic acid could also attenuate isoprenaline-induced mouse heart fibrosis and cell apoptosis by reducing oxidative stress, inflammation, and apoptosis in vivo. Conclusions We proved that ferulic acid protects cardiomyocytes from oxidative stress-induced injury by regulating the miR-499-5p/p21signaling pathway, which provides insight into the clinical application of ferulic acid in the treatment of cardiovascular diseases.
Highlights
Cardiovascular disease (CVD) is the main cause of death worldwide
Many cardiovascular diseases can lead to mitochondrial function impairment or loss in cardiomyocytes and cause a chronic increase in reactive oxygen species (ROS) production and retention of antioxidant function, which leads to catastrophic positive feedback of mitochondrial DNA damage and more ROS generation [4]
Excessive ROS production can directly damage the expression and Evidence-Based Complementary and Alternative Medicine function of key proteins that are involved in the excitationcontraction coupling of cardiomyocytes and the activation of a variety of proinflammatory signal kinases and transcription factors, which lead to cardiomyocyte injury and apoptosis [5]
Summary
Cardiovascular disease (CVD) is the main cause of death worldwide. With the increase in the aging population, the mortality rate caused by cardiovascular disease is on the rise [1], with more than 17 million people dying every year worldwide. Oxidative stress, defined as excessive production of reactive oxygen species (ROS) and a disturbance between ROS and antioxidants, has been shown to cause cumulative damage and to play an important role in the development of cardiovascular diseases, such as heart failure, heart infarction and ischemia, and heart remodeling [3]. Excessive ROS production can cause cell dysfunction, protein and lipid peroxidation, and DNA damage, which may lead to irreversible cell damage and death and a variety of cardiovascular diseases [3]. Many cardiovascular diseases can lead to mitochondrial function impairment or loss in cardiomyocytes and cause a chronic increase in ROS production and retention of antioxidant function, which leads to catastrophic positive feedback of mitochondrial DNA (mtDNA) damage and more ROS generation [4]. ROS can stimulate cardiac fibroblast proliferation and matrix metalloproteinase activation, leading to increases in extracellular matrix and heart remodeling [5]. erefore, it is very important to find new drugs to inhibit oxidative stress for the treatment of cardiovascular diseases
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