Down-regulation of Syvn1 alleviates myocardial ischemia-reperfusion injury in mice by activating PPARα signaling to prevent oxidative stress

Ischemic heart disease, as one of the major causes of morbidity and mortality in the world, has become a predictive risk factor for adverse cardiovascular events. Despite recent advances, there is no effective therapy for preventing myocardial ischemia-reperfusion injury (MIRI). Synoviolin1 (Syvn1) is an E3 ubiquitin ligase that is thought to participate in the pathological process of ischemic heart disease. However, the expression and function of Syvn1 have not been fully elucidated in MIRI. Here, we investigated its effects on cardiac function and oxidative stress status in a mouse model of MIRI. In this study, our results showed that downregulation of Syvn1 expression prevented the MIRI-induced increases in infarct size, serum creatine kinase (CK), and lactate dehydrogenase (LDH), and protected cardiac function in mice. Furthermore, downregulation of Syvn1 was found to decrease the levels of parameters reflecting oxidative stress, such as dihydroethidium (DHE), malondialdehyde (MDA), and nitric oxide (NO), while increasing the levels of parameters reflecting antioxidants, such as total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD) in MIRI-induced ischemic cardiac tissues. Of note, I/R stimulation reduced peroxisome proliferator activated receptor α (PPARα) expression in ischemic cardiac tissues, which was partially prevented by downregulation of Syvn1. Furthermore, application of the PPARα inhibitor GW6471 partially abolished the protective effects of downregulation of Syvn1 on oxidative stress and cardiac function in MIRI mice. Collectively, these results highlight the important function of Syvn1 in MIRI and provide a potential target for clinical treatment and prognosis of MIRI.