MiR-129-5p Protects H9c2 Cardiac Myoblasts From Hypoxia/Reoxygenation Injury by Targeting TRPM7 and Inhibiting NLRP3 Inflammasome Activation.

ABSTRACT: As a biomarker for heart failure, miR-129-5p is abnormally expressed during myocardial I/R, but its specific functions and mechanisms remain largely unclear. Thus, this study explored the roles and possible mechanisms of miR-129-5p in hypoxia/reoxygenation (H/R)-insulted H9c2 cardiac myoblasts. After H/R insult, miR-129-5p expression levels were decreased, along with reduced cell viability and enhanced lactate dehydrogenase release in H9c2 cells. Overexpression of miR-129-5p through transfection of miR-129-5p mimics effectively improved cell viability and reduced lactate dehydrogenase release in H9c2 cells exposed to H/R, along with decreased apoptosis and caspase-3 activities. Moreover, miR-129-5p mimics inhibited reactive oxygen species production and upsurged superoxide dismutase activity in H9c2 cells exposed to H/R, and suppressed H/R-caused massive release of proinflammatory cytokines TNF-α and IL-1ß. TRPM7 was identified as the target of miR-129-5p and was negatively regulated by miR-129-5p. TRPM7 overexpression counteracted the antagonistic effect of miR-129-5p on H/R-induced increase in intracellular calcium levels. TRPM7 overexpression also abolished miR-129-5p-induced elevation on cell viability and reduction on apoptosis as well as attenuated miR-129-5p-induced inhibition on reactive oxygen species and IL-1ß production. Besides, H/R-induced NLRP3 inflammasome activation was inhibited by miR-129-5p mimic but reactivated by TRPM7. In conclusion, miR-129-5p alleviates H/R injury of H9c2 cardiomyocytes by targeting TRPM7 and inhibiting NLRP3 inflammasome activation, suggesting that miR-129-5p and TRPM7 may be potential therapeutic targets for myocardial I/R injury.

Two cases of non-intervention-related vascular intense spasm following stent implantation in the coronary artery.

The clinical occurrence of non-intervention-related vascular spasm following coronary stenting is rare. In the present study, 2 cases are reported. One patient developed continuous spasms in the proximal segment of the left anterior descending (LAD) and left circumflex (LCX) arteries following LAD artery stenting. The second patient developed an intense spasm in the right coronary artery (RCA) following LAD artery stenting. Clinical course and prognosis are dangerous. The main treatment for this condition is a combination of repeated injections of nitroglycerin into the coronary artery and the administration of calcium antagonists. In the clinic, intervention-related vascular spasms are common in percutaneous coronary intervention (PCI) due to the mechanical stimulation caused by balloon dilatation or stent expansion. Injections of a vasodilator into the coronary artery are able to mitigate the spasms and the consequent prognosis is good.

Estrogen treatment inhibits vascular endothelial senescence and asymmetrical dimethylarginine in ovariectomized rabbits.

To investigate the effects of estrogen treatment on aortic endothelial senescence and atherosclerosis, an ovariectomized female rabbit model was constructed, and human umbilical vein endothelial cells were utilized to explore the potential mechanisms. Twenty-eight female rabbits were randomized into 4 groups (7 each): sham operation, ovariectomized, ovariectomized plus low-dose estradiol treatment, and ovariectomized plus high-dose estradiol treatment. All rabbits were fed on high-cholesterol diet for 12 weeks. Blood samples were collected to determine the serum estradiol, asymmetric dimethyl L-arginine (ADMA), and lipid levels, and the aortas were separated for histopathologic analysis. After ovariectomy and high-fat diet, the concentration of serum estradiols declined significantly (P < 0.01) and the levels of ADMA and serum lipids increased (all P < 0.01) as the area of senescent endothelium and atherosclerotic lesions enlarged (both P < 0.01). However, administration of estradiols reduced the levels of ADMA, total cholesterol, and low-density lipoprotein (LDL) cholesterol and inhibited endothelial senescence and atherosclerosis (all P < 0.01). Simultaneously, the concentration of high-density lipoprotein cholesterol and triglyceride increased (all P < 0.01). In vitro experiments also confirmed that estradiols could decrease the ADMA levels induced by oxidized LDL and inhibited oxidized LDL­induced and ADMA-induced human umbilical vein endothelial cell senescence. These results indicate that estrogens can inhibit endothelial senescence and atherosclerosis with reduced ADMA levels and improved lipid profile.

[Effect of estrogen replacement therapy in the early phase on atherosclerosis and PAI-1 in ovariectomized cholesterol-fed rabbit].

OBJECTIVE: To investigate the effect of estrogen replacement therapy (ERT) in the early phase on the atherosclerosis and the level of plasminogen activator inhibitor-1(PAI-1). METHODS: Twenty-eight rabbits were randomly assigned to 4 groups: Group A, sham operation (n=7); Group B, ovariectomized without estradiol (n=7); Group C, ovariectomized with low-dose estradiol (n=7); and Group D, ovariectomized with high-dose estradiol (n=7). All rabbits were given 1% cholesterol diet for 12 weeks. Levels of blood lipid, estradiol, and PAI-1 were measured before the operation and at the end of the 4th and 12th weeks. Twelve weeks later, we took the aortas for pathological analysis and calculated the areas of atherosclerotic plaque. RESULTS: After 12 weeks, the estradiol level of Group B was significantly lower than that of Group A, and that of Group D was obviously higher than Group A. There was no significant difference between Group C and A. The concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in Group B significantly increased compared with Group A (P<0.01). The levels of TC and LDL-C of Group C and D were significantly lower than those of Group A. Whereas the concentrations of triglyceride (TG) and high density lipoprotein cholesterol (HDL-C) in Group B were lower than those of Groups A, C and D (P<0.01). In contrast to Groups A, C and D, the level of PAI-1 was significantly higher in the Group B (P<0.01), without significant differences among Groups A, C and D. The area of atherosclerotic lesion of aorta in Group B was significantly bigger than that of Group A, C and D. The areas of aortic atherosclerotic plaque in Group C and D were obviously smaller than those of Group A (P<0.01). CONCLUSION: Transdermal estrogen replacement therapy in the early phase can improve the metabolism of the serum lipids, reduce the level of PAI-1, and probably provide the protective effect on the atheroma formation.