Key result
The mitochondrial-targeted H2S donor AP39 inhibited mitochondrial autophagy through the PINK1/Parkin pathway, antagonized myocardial cell iron death, and improved myocardial fibrosis in rats with myocardial infarction.
Why the study?
Mitochondrial autophagy and iron death are involved in the pathogenesis of myocardial fibrosis, but whether the mitochondrial-targeted H2S donor AP39 acts through the PINK1/Parkin pathway to improve post-infarction myocardial fibrosis was unknown.
Does AP39 improve myocardial fibrosis and inhibit ferroptosis in models of myocardial infarction?
Does AP39 improve myocardial fibrosis and inhibit ferroptosis in models of myocardial infarction?
The mitochondrial-targeted H2S donor AP39 improves myocardial fibrosis after myocardial infarction by inhibiting mitochondrial autophagy and ferroptosis via the PINK1/Parkin pathway in preclinical models.
AP39 may reduce post-MI fibrosis via ferroptosis inhibition in animals; leaves open translation to human therapy.
Research has revealed the involvement of mitochondrial autophagy and iron death in the pathogenesis of myocardial fibrosis. The objective of this study is to investigate whether the mitochondrial-targeted H2S donor AP39 inhibits mitochondrial autophagy and antagonizes myocardial cell iron death through the PINK1/Parkin pathway, thereby improving myocardial fibrosis in rats with myocardial infarction. A rat model of myocardial infarction was created by intraperitoneal injection of a high dose of isoproterenol, and H9c2 myocardial cells were subjected to hypoxic injury induced by CoCl2. Western blot, RT-PCR, transmission electron microscopy, immunohistochemistry, as well as echocardiography, and studies on isolated hearts were employed. In the hearts of rats with myocardial infarction, there was a significant accumulation of interstitial collagen fibers, accompanied by downregulation of CSE protein expression, activation of the PINK1/Parkin signaling pathway, and activation of mitochondrial autophagy. Intervention with AP39 resulted in a significant improvement of the aforementioned changes, which could be reversed by the addition of PAG. Similar results were observed in vitro experiments. Furthermore, the addition of CCCP reversed the antagonistic effect of AP39 on myocardial cell iron death, while the addition of RSL3 reversed the inhibitory effect of AP39 on collagen production in myocardial cells. The mitochondrial-targeted H2S donor AP39 can inhibit mitochondrial autophagy through the PINK1/Parkin pathway, antagonize myocardial cell iron death, and improve myocardial fibrosis in rats with myocardial infarction.
No takes yet. Share an insight, caveat, or question.
Yang et al. (2023) studied Myocardial fibrosis with myocardial infarction. AP39 was evaluated on Myocardial fibrosis, mitochondrial autophagy, and myocardial cell iron death. The mitochondrial-targeted H2S donor AP39 inhibited mitochondrial autophagy through the PINK1/Parkin pathway, antagonized myocardial cell iron death, and improved myocardial fibrosis in rats with myocardial infarction.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: