lncRNA­MALAT1 promotes high glucose­induced H9C2 cardiomyocyte pyroptosis by downregulating miR­141­3p expression.

Diabetic cardiomyopathy (DCM) is caused by diabetes and can result in heart failure. Long non­coding RNAs (lncRNAs) have been demonstrated to be closely associated with DCM development. The present study aimed to investigate whether lncRNA­metastasis­associated lung adenocarcinoma transcript­1 (MALAT1) altered high glucose (HG)­induced H9C2 cardiomyocyte pyroptosis by targeting microRNA (miR)­141­3p. H9C2 cells were treated with normal glucose (NG) or HG. lncRNA­MALAT1 and miR­141­3p expression levels were determined via reverse transcription­quantitative PCR (RT­qPCR). MALAT1 and miR­141­3p knockdown and overexpression were established and confirmed via RT­qPCR. The association between MALAT1 expression and miR­141­3p expression, as well as the induction of pyroptosis and gasdermin D (GSDMD)­N expression were evaluated by performing dual luciferase reporter, TUNEL staining and immunofluorescence staining assays, respectively. Western blotting was conducted to measure the expression levels of pyroptosis­associated proteins, including apoptosis­associated speck­like protein, GSDMD­N, caspase­1, nucleotide oligomerization domain­like receptor protein 3 and GSDMD. MALAT1 mRNA expression levels were significantly increased, whereas miR­141­3p expression levels were significantly decreased in HG­treated H9C2 cells compared with the NG group. Compared with the HG group, MALAT1 overexpression significantly reduced miR­141­3p expression levels, increased the rate of TUNEL positive cells and upregulated the expression levels of pyroptosis­associated proteins. MALAT1 knockdown displayed the opposite effect on the rate of TUNEL positive cells and the expression levels of pyroptosis­associated proteins. Furthermore, the rate of TUNEL positive cells, and GSDMD­N and pyroptosis­associated protein expression levels were significantly reduced by miR­141­3p overexpression in MALAT1­overexpression H9C2 cells. The results indicated that compared with NG treatment, HG treatment increased MALAT1 expression levels and decreased miR­141­3p expression levels in H9C2 cells. Therefore, the present study suggested that lncRNA­MALAT1 targeted miR­141­3p to promote HG­induced H9C2 cardiomyocyte pyroptosis.

[Prevention of rupture of atherosclerotic plaque by Candesartan in rabbit model].

OBJECTIVE: To evaluate Candesartan therapeutic effect against atherosclerotic plaque rupture and to explore the related mechanisms. METHODS: Thirty-four New Zealand White male rabbits were randomly divided into three groups: the control group, the model control group and the Candesartan intervention group. The control group rabbits were fed with a normal diet. Rabbits of the latter two groups were fed with a 1% high-cholesterol diet and received a balloon catheter injury respectively one week after the cholesterol feeding. Candesartan (0.5 mgⁱkg⁻¹â±d⁻¹) was given to the Candesartan group rabbits 2 days before the performance of the balloon catheter injury. By the end of 12(th) week of the experiment, Russell's viper venom was used for rabbits of both the model control and the Candesartan groups in order to induce rupture of the plaques developed and followed by sacrifice of all the rabbits of the 3 groups. The aortas were removed and fixed for histological evaluation. Immunohistochemistry of MMP-9, macrophage markers and collagen were performed. The protein expression of MMP-9 was determined using Western blot analysis. RESULTS: In the model control group, 7 of 9 rabbits with a total of 12 plaques developed rupture and thrombosis of the plaques after the induction. In contrast, only 2 of 10 rabbits with a total of 3 plaques demonstrated rupture and thrombosis in the Candesartan group (P < 0.05). The control group rabbits did not have plaque rupture and thrombosis. Compared with the model group, both the percentage area of MMP-9 and macrophages in the plaques were significantly decreased in the Candesartan group (12.35% ± 4.28% vs 32.58% ± 9.16%, P < 0.05; 13.87% ± 4.91% vs 23.8% ± 7.45%, P < 0.05). There was an increased percentage of collagen content in total plaques of the Candesartan group (30.27% ± 11.36% vs 4.18% ± 1.28%, P < 0.01). Compared with the model group, the protein expression of MMP-9 was significantly decreased in the Candesartan group (P < 0.01). CONCLUSION: Candesartan has a preventive value against atherosclerotic plaque rupture in hypercholesterolemic rabbits, likely through its reduction of MMP-9 expression, inhibition of macrophage accumulation and increase of collagen content within the plaques.