RESUMEN
Myocardial infarction (MI) is a fatal heart disease that affects millions of lives worldwide each year. This study investigated the roles of HIF-1α/lncRNA-TUG1 in mitochondrial dysfunction and pyroptosis in MI. CCK-8, DHE, lactate dehydrogenase (LDH) assays, and JC-1 staining were performed to measure proliferation, reactive oxygen species (ROS), LDH leakage, and mitochondrial damage in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Enzyme-linked immunoassay (ELISA) and flow cytometry were used to detect LDH, creatine kinase (CK), and its isoenzyme (CK-MB) levels and caspase-1 activity. Chromatin immunoprecipitation (ChIP), luciferase assay, and RNA-immunoprecipitation (RIP) were used to assess the interaction between HIF-1α, TUG1, and FUS. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were used to measure HIF-1α, TUG1 and pyroptosis-related molecules. Hematoxylin and eosin (HE), 2,3,5-triphenyltetrazolium chloride (TTC), and terminal deoxynucleotidyl transferase dUTP risk end labelling (TUNEL) staining were employed to examine the morphology, infarction area, and myocardial injury in the MI mouse model. Mitochondrial dysfunction and pyroptosis were induced in H/R-treated cardiomyocytes, accompanied by an increase in the expression of HIF-α and TUG1. HIF-1α promoted TUG1 expression by directly binding to the TUG1 promoter. TUG1 silencing inhibited H/R-induced ROS production, mitochondrial injury and the expression of the pyroptosis-related proteins NLRP3, caspase-1 and GSDMD. Additionally, H/R elevated FUS levels in cardiomyocytes, which were directly inhibited by TUG1 silencing. Fused in sarcoma (FUS) overexpression reversed the effect of TUG1 silencing on mitochondrial damage and caspase-1 activation. However, the ROS inhibitor N-acetylcysteine (NAC) promoted the protective effect of TUG1 knockdown on H/R-induced cardiomyocyte damage. The in vivo MI model showed increased infarction, myocardial injury, ROS levels and pyroptosis, which were inhibited by TUG1 silencing. HIF-1α targeting upregulated TUG1 promotes mitochondrial damage and cardiomyocyte pyroptosis by combining with FUS, thereby promoting the occurrence of MI. HIF-1α/TUG1/FUS may serve as a potential treatment target for MI.
RESUMEN
OBJECTIVE: The aim of this study was to investigate the correlations between risk factors such as hypertension and the complex degrees of coronary arterial lesions (CAL). METHODS: We selected 462 patients with coronary heart disease (CHD) with confirmed the stenosis (≥50 %) in at least one major coronary artery on coronary angiography and divided them into the "CHD with hypertension" group (CHD-HT, n = 306) and the CHD group (n = 156). The characteristics of CAL and the occurrence of 2-year postoperative major adverse cardiac cerebrovascular events (MACCE) in the two groups were observed. RESULTS: The mean SYNTAX scores (SS) was higher in the CHD-HT group than in the CHD group (P < 0.05). The proportions of complex, calcified, and diffused long lesions in the PCI patients' target vascular lesions, as well as the total MACCE incidence, were significantly higher in the CHD-HT group than in the CHD group (P < 0.05). Logistic multifactor regression analysis showed that age, male sex, hypertension, diabetes, hyperlipidemia, and previous history of myocardial infarction were positively correlated with the SS (P < 0.05). CONCLUSIONS: The patients with CHD-HT exhibited complicated and diffused CAL, and arterial hypertension can be considered as a risk factor for the complexity of coronary lesions in patients with ischemic heart disease.