Role of AIM2 Gene Knockdown Mechanism in Diabetic Cardiomyopathy: an In Vivo and Ex Vivo Study.

Chronic hyperglycemia induces reactive oxygen species that have an essential function in tissue injuries in cases of diabetic cardiomyopathy. The mechanism of the absent in melanoma 2 (AIM2)-associated inflammasome response in diabetic cardiomyopathy is unknown. Therefore, this study was performed to investigate the role of AIM2 and its molecular mechanisms. Diabetic rats received 1 × 108 viral injections of 5'-GGTCACCAGTTCCTCAGTT-3' (n = 15) or 5'-TTCTCCGAACGTGTCACGT-3' (negative control group, n = 15). Normal rats (n = 15) and diabetic rats (n = 15) were also included in the experiment. Ex vivo study was performed on primary cardiomyocytes for different concentrations of glucose. AIM2 inhibition did not affect any of the metabolic parameters (p > 0.05 for all). AIM2 protein levels were significantly increased in rats with diabetes mellitus compared with those in the control group (p < 0.0001, q = 32.044). Also, viral injection (sequence: 5'-GGTCACCAGTTCCTCAGTT-3') decreased the diabetes mellitus-induced increase in expression of AIM2 protein levels (p < 0.0001, q = 27.129). Cardiac dysfunctions were reported in rats with diabetes mellitus characterized by several parameters (p < 0.01 for all). The diabetic myocardium of rats was reported to have higher deposits of extracellular matrix compared to the control rats (p < 0.001). These effects were downregulated by viral injection (sequence: 5'-GGTCACCAGTTCCTCAGTT-3'). Ex vivo research revealed that high glucose concentrations significantly increased AIM2 protein expression, reactive oxygen species, and cell death. AIM2 protein in diabetic cardiomyopathy is associated with reactive oxygen species production and cardiomyocyte death.

miR-211-5p Alleviates the Myocardial Ischemia Injury Induced by Ischemic Reperfusion Treatment via Targeting FBXW7.

Cardiovascular diseases, a class of the most common diseases, seriously threaten human health, which is a direct inducement of death in most countries. The restoration of blood supply is an impactful intervention way for cardiovascular disease treatments while the injury induced by oxygen-glucose deprivation and ischemic reperfusion (I/R) may further impact the tissues of the patients. Myocardial reperfusion is a precondition for saving ischemic myocardial tissues in acute myocardial infarction while the injury induced by immediate reperfusion takes a great challenge for cardiovascular disease treatment. Howbeit, the reperfusion of coronary blood could aggravate the injury triggered by ischemia. At present, several studies have focused on the etiopathogenesis and therapeutic strategies of ischemia-reperfusion injury of the myocardium. The report has verified that miR-211-5p was elevated in the pathological specimens, while the influence of miR-211-5p in I/R-mediated injury of myocardial cells remains unclear. This research is aimed at illustrating the role of miR-211-5p in the progression of I/R injury of myocardial cells, and qRT-PCR, western blot, CCK-8, and TUNEL assay were used to investigate the functions of miR-211-5p on I/R-mediated injury of myocardial cells. The result mirrored that miR-211-5p was distinctly reduced in the I/R-induced AC16, and reduced miR-211-5p could evidently improve the viability of I/R-induced AC16. miR-211-5p could directly target FBXW7, and FBXW7 upregulation could reverse the improvement of AC16 in viability and apoptosis level after suffering I/R. Moreover, it was also proved that miR-211-5p can mediate the activation of Wnt/ß-catenin via attenuating FBXW7. Consequently, this investigation identified miR-211-5p as a positive role to attenuate the injury of myocardial cells when suffering I/R treatment.