Abstract
Post-myocardial infarction heart failure (post-MI HF) is one of the leading global causes of death, and current prevention and treatment methods still cannot avoid the increasing incidence. Honokiol (HK) has previously been reported to improve myocardial ischemia/reperfusion injury and reverse myocardial hypertrophy by activating Sirt1 and Sirt3. We suspect that HK may also have a therapeutic effect on post-MI HF. In this study, we aimed to investigate the efficacy and mechanism of HK in the treatment of post-MI HF. We found that HK inhibited myocardial reactive oxygen species (ROS) production, reduced myocardial fibrosis, and improved cardiac function in mice after MI. HK also reduced the abnormality of mitochondrial membrane potential (MMP) and apoptosis of cardiomyocytes caused by peroxide in neonatal cardiomyocytes. RNAseq results revealed that HK restored the transcriptome changes to a certain extent and significantly enhanced the expression of mitochondrial inner membrane uncoupling protein isoform 3 (Ucp3), a protein that inhibits the production of mitochondrial ROS, protects cardiomyocytes, and relieves heart failure after myocardial infarction (MI). In cardiomyocytes with impaired Ucp3 expression, HK cannot protect against the damage caused by peroxide. More importantly, in Ucp3 knockout mice, HK did not change the increase in the ROS level and cardiac function damage after MI. Taken together, our results suggest that HK can increase the expression of the cardioprotective protein Ucp3 and maintain MMP, thereby inhibiting the production of ROS after MI and ameliorating heart failure.
Highlights
Heart failure (HF) is one of the leading global causes of death, with about 64.3 million patients currently living with HF worldwide (Shah et al, 2017; Disease et al, 2018)
We report that HK can increase uncoupling protein isoform 3 (Ucp3) levels
We showed that honokiol emulsion (HKE) treatment prevented the induction of cardiac fibrosis and reduced cardiac hypertrophy
Summary
Heart failure (HF) is one of the leading global causes of death, with about 64.3 million patients currently living with HF worldwide (Shah et al, 2017; Disease et al, 2018). 70% of all HF syndromes can be attributed to underlying ischemic heart disease, which plays a pivotal role in the development and progression of HF with reduced and preserved ejection fraction (EF) (Elgendy et al, 2019). Since the mammalian heart has negligible regenerative capacity, the death of large numbers of cardiomyocytes results in their replacement with a non-contractile, collagen-based scar that maintains the structural integrity of the ventricle and prevents catastrophic events, such as cardiac rupture (Frangogiannis, 2015)
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