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The aim of the present study was to investigate hypoxia-induced apoptosis and autophagy in vascular smooth muscle cells (VSMCs) and the underlying molecular mechanisms of microRNA (miR)-17-5p responses in an anaerobic environment. The results revealed that miR-17-5p expression was significantly upregulated in VSMCs subjected to hypoxic conditions (P<0.05) and lower miR-17-5p levels were observed in ethyl 3,4-dihydroxybenzoate-treated and hypoxia inducible factor-1 loss-of-function cells. Additionally, it was demonstrated that miR-17-5p is associated with hypoxia-induced autophagy, which was confirmed by upregulating the light chain 3-II/LC3-I ratio and downregulating nucleoporin p62. Cell apoptosis was inhibited in response to hypoxia, and levels of pro-apoptotic proteins B-cell lymphoma 2-associated X protein and p-caspase were markedly decreased when VSMCs were subjected to hypoxic conditions. Furthermore, expression of signal transducer and activator of transcription 3 (STAT3) decreased when cells were transfected with overexpressing miR-17-5p and subjected to hypoxic conditions, and the combination of miR-17-5p loss-of-function and hypoxia induced greater upregulation in the protein expression of STAT3 compared with a single treatment for hypoxia in VSMCs. In conclusion, miR-17-5p may be a novel hypoxia-responsive miR and hypoxia may induce protective autophagy and anti-apoptosis in VSMCs by targeting STAT3.

To explore the mechanism of jatrorrhizine on apoptosis and fibrosis induced by myocardial infarction (MI) in an animal model. Methods: The left anterior descending branch of coronary artery was surgically ligated to duplicate the mouse model of MI. The sham and infarcted mice were treated with normal saline once a day, while mice in experimental groups received low-dose (LD) and high-dose (HD) jatrorrhizine once a day respectively. Two weeks later, cardiac function was detected by echocardiography, and histopathological examination was performed using hematoxylin and eosin (H&E) and Masson staining. The expressions of p53, TGF-β1, Smad/2/3, Bax, Bcl-2, collagen I and collagen III were quantified using qRT-PCR and western blot assays.Results: Jatrorrhizine significantly improved left ventricular ejection fraction (LVEF) and left ventricle end-systolic (LVES) in mice.Histopathological, administration of jatrorrhizine weakened infiltration of inflammatory cells and cardiac fibrosis in myocardium of mice caused by MI. Additionally, jatrorrhizine suppressed cardiomyocyte apoptosis exhibited as its capability to reverse changes of Bax and Bcl-2 levels in myocardium caused by MI. Jatrorrhizine statistically significantly downregulated expression of collagen I and collagen III, as well as TGF-β1, Smad2/3 and p53. Conclusion: Jatrorrhizine reduce cardiomyocyte apoptosis and fibrosis through inhibiting p53/Bax/Bcl-2 and TGF-β1/Smad2/3 signaling pathways.

Acute myocardial infarction is one of the major leading causes for heart failure, which can lead to the irreversible loss of cardiomyocytes and impaired cardiac function. Hence, the efficient therapeutic agents are still urgent. Our study aimed to explore the role of a natural isoquinoline alkaloid, palmatine, in an acute myocardial infarction mouse model. In this study, intragastric administrated palmatine significantly enhanced left ventricle ejection fraction and left ventricle end-systolic of infarcted mice heart. Meanwhile, palmatine administration partially recovered myocardial structure and attenuated the cardiac fibrosis and infiltration of inflammatory cells. In addition, the usage of palmatine further enhanced the increased transforming growth factor (TGF)-beta1 level, reduced the elevated tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta level in the myocardium of acute myocardial infarction–induced mice, as well as elevated the reduced superoxide dismutase production and inhibited the increased malondialdehyde secretion in infarcted myocardium of mice. Meanwhile, acute myocardial infarction led the significant upregulation of Bcl-2-associated X and downregulation of B-cell lymphoma-2 in the myocardium, and palmatine administration statistically enabled to recover the expression changes of these two apoptosis-related proteins. Moreover, palmatine administration obviously elevated the expression levels of phosphorylated AMP-activated protein kinase and nuclear factor erythroid 2–related factor 2 in the myocardium of acute myocardial infarction–induced mice. In a word, our study indicated that palmatine could protect infarcted myocardium of mice from apoptosis, inflammation, and oxidative stress. Our results suggested that palmatine might be a novel therapeutic agent for acute myocardial infarction. Graphical Abstract