Role of thioredoxin-interacting protein-mediated inflammatory response and apoptosis in myocardial infarction

doi:10.12307/2023.116

Abstract

Abstract: BACKGROUND: In recent years, studies have found that the expression of thioredoxin-interacting protein is increased in the myocardial tissue of mice with myocardial infarction. Thioredoxin-interacting protein is the endogenous activator of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome. It is unclear whether it participates in the pathological process of myocardial infarction by activating the inflammasome.
OBJECTIVE: To investigate the effects of thioredoxin-interacting protein on cardiomyocyte apoptosis and NLRP3 inflammasomes, thereby providing new ideas for the prevention and treatment of myocardial infarction.
METHODS: A total of 30 thioredoxin-interacting protein knockout mice and 30 wild-type littermate C57BL/6 mice were selected and randomly divided into myocardial infarction group and sham operation group with 15 mice in each group. Myocardial infarction models were established. Four days after the operation, some mice (10 mice in each group) were sacrificed and the heart tissue was collected. TdT-mediated dUTP nick end labeling was used to detect cardiomyocyte apoptosis in mice (5 mice in each group). Western blot (5 mice in each group) was used to detect the expression of thioredoxin-interacting protein, NLRP3, cleaved cysteinyl aspartate specific proteinase-1, apoptosis-associated speck-like protein containing CARD, cleaved interleukin-1β, and cleaved cysteinyl aspartate speacific proteinase-3. The remaining mice (5 mice in each group) were fed till 1 month after the operation. The cardiac function was detected by echocardiography before the mice were sacrificed and heart tissue samples were collected for later use.
RESULTS AND CONCLUSION: The expression level of thioredoxin-interacting protein was significantly upregulated in the wild-type myocardial infarction group than the wild-type sham operation group (P < 0.05). Compared with the sham operation groups, the expressions of NLRP3, cleaved cysteinyl aspartate specific proteinase-1, apoptosis-associated speck-like protein containing CARD, cleaved interleukin-1β, and cleaved cysteinyl aspartate specific proteinase-3 proteins in the myocardium were significantly upregulated in the two myocardial infarction groups (P < 0.05). Compared with the wild-type myocardial infarction group, the expression levels of the above-mentioned five proteins were significantly downregulated, the cardiomyocyte apoptosis was reduced, and the cardiac function was significantly improved in the thioredoxin-interacting protein knockout mice with myocardial infarction (P < 0.05). To conclude, thioredoxin-interacting protein knockout can inhibit the expression of NLRP3, cleaved cysteinyl aspartate specific proteinase-1, apoptosis-associated speck-like protein containing CARD, cleaved interleukin-1β, and cleaved cysteinyl aspartate specific proteinase-3 proteins, reduce cardiomyocyte apoptosis, and thereby improve cardiac function after myocardial infarction. It is expected to provide a target for the clinical treatment of myocardial infarction.

Key words: thioredoxin-interacting protein, gene knockout, myocardial infarction, cardiomyocyte apoptosis, NLRP3 inflammasome

CLC Number:

Wang Xuejiao, Shi Wenjuan, Zhang Yan, Xing Dehai, Li Dongxue, Jiao Xiangying. Role of thioredoxin-interacting protein-mediated inflammatory response and apoptosis in myocardial infarction[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(11): 1715-1721.

Figures/Tables 6

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