Astaxanthin protecting myocardial cells from hypoxia/reoxygenation injury by regulating miR-138/HIF-1α axis.

OBJECTIVE: To investigate astaxanthin (AST) protecting myocardial cells from hypoxia/reoxygenation (H/R) injury by regulating miR-138/HIF-1α axis. MATERIALS AND METHODS: Myocardial cells were collected and divided into a control group, a H/R group, and a H/R+AST group. The H/R injury model was established, and cells in the H/R+AST group were given AST before modeling. The cell survival rate, contents of myocardial enzymes, and apoptosis were detected. RESULTS: The survival rate in the H/R group reduced and was lower than that in the H/R+AST group (p<0.05). Compared with the control group, activities of myocardial enzymes significantly increased in the H/R group but those were inhibited in the H/R+AST group (p<0.05). The apoptotic rate in the H/R group significantly increased compared with the control group but that significantly decreased compared with the H/R+AST group (p<0.05). The expression of cleaved caspase-9 and caspase-3 increased in the H/R group (p<0.05), and was higher than that in the H/R+AST group (p<0.05). The expression levels of miR-138 and HIF-1α were detected. MiR-138 level significantly decreased in the H/R group but increased in the H/R+AST group (p<0.05). Compared with the control group, HIF-1α content significantly increased in the H/R group but that was significantly inhibited in the H/R+AST group (p<0.05). The Luciferase reporter gene assay confirmed that HIF-1α was the target gene of miR-138. After miR-138 mimics and HIF-1α siRNA were transfected into myocardial cells, the cell survival rate significantly increased, and activities of myocardial enzymes were significantly inhibited in the H/R+AST+miR-138 mimics and H/R+AST+HIF-1α siRNA groups (p<0.05). The apoptotic rate significantly decreased, and contents of cleaved caspase-9 and caspase-3 were significantly inhibited in the miR-138 mimics and HIF-1α siRNA groups (p<0.05). CONCLUSIONS: AST can exert a protective function in myocardial cells via regulating the expression of miR-138/HIF-1α axis.

Rosuvastatin inhibits inflammatory response and resists fibrosis after myocardial infarction.

OBJECTIVE: To study the effect of rosuvastatin on myocardial infarction in rats and its mechanism of action. MATERIALS AND METHODS: 24 Sprague-Dawley (SD) rats were randomly divided into 3 groups: intensive statin group (n=8), myocardial infarction control group (n=8) and sham-operation group (n=8). The left anterior descending coronary artery was ligated to establish myocardial infarction models. Rats in intensive statin group were treated with gavage via rosuvastatin (1 mg × kg) and 1.5 mL distilled water suspension at 3 d before operation, while rats in the other two groups received gavage via the same amount of distilled water till 4 weeks after operation. Venous blood was collected using capillary glass tubes at 3 d before operation (before medication) and the last day in the 4th week after operation. Interleukin-6 (IL-6) was detected via chemiluminescence assay, and tumor necrosis factor-α (TNF-α) was detected via immunofluorescence assay. Hematoxylin and eosin (HE) staining and Masson staining were performed for myocardium to detect the inflammation and fibrosis. Finally, the expressions of inflammatory protein p65, peroxisome proliferator-activated receptor (PPAR) and fibrin were detected via Western blotting, and the Snail expression was detected by immunohistochemical assay. RESULTS: The survival rate and cardiac function of rats in intensive statin group were superior to those in control group. HE staining and detection of blood IL-6 and TNF-α, and p65 and PPAR protein expressions revealed that the inflammatory levels in the body and myocardium of rats in intensive statin group were decreased compared with those in control group. Masson staining and detection of fibrin level showed that the myocardial fibrosis level of rats in intensive statin group was reduced compared with that in control group. CONCLUSIONS: Rosuvastatin can reduce the level of myocardial fibrosis through alleviating the inflammatory response in rats with myocardial infarction.

Effects of rosuvastatin on pentraxin 3 level and platelet aggregation rate in elderly patients with acute myocardial infarction undergoing elective interventional therapy: a double-blind controlled study.

OBJECTIVE: To investigate clinical effects of rosuvastatin on blood lipid levels, hemorheological profiles, vascular endothelial function, pentraxin 3 (PTX-3) level, the number of granule membrane glycoprotein (GMP-140) molecules and platelet aggregation rate in elderly patients with acute myocardial infarction (AMI) undergoing elective percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Total of 120 elderly patients admitted with AMI undergoing elective PCI from July 2014 to January 2016 were selected. The patients were divided into the control group and the experimental group based on the rule of random number generation and double-blind controlled trial, 60 cases in each group. All of 120 patients were treated with routine medications; the experimental group was orally administered with rosuvastatin 1 week before PCI. Blood lipid levels, hemorheological profiles, vascular endothelial function, PTX-3, the number of GMP-140 molecules and platelet aggregation rate were compared between two groups before treatment with rosuvastatin and 10d after elective PCI. RESULTS: Triglycerides, plasma total cholesterol, and low-density lipoprotein levels were significantly lower (p<0.05) in the experimental group when compared with the control group; plasma viscosity, fibrinogen, the viscosity of blood in the high shear rates and in the low shear rates in the experimental group were significantly lower than those of the control group (p<0.05); FMD and NMD in the experimental group were significantly higher than those of the control group (p<0.05); ET-1, TXA2 levels in the experimental group were lower, however, PGI2, NO as well as NOS in the experimental group were higher, when compared the control group, the differences were statistically significant (p<0.05); PTX-3, the number of GMP-140 molecules and platelet aggregation rate in the experimental group were significantly lower than those of the control group (p<0.05). CONCLUSIONS: Oral administration of rosuvastatin 1 week before PCI can significantly improve the blood lipid levels and hemorheological profiles, enhance endothelial function, reduce the PTX-3 level and the number of GMP-140 molecules, decrease the platelet aggregation rate, therefore improving prognosis in elderly patients with AMI undergoing PCI.