Knockdown of hypoxia-inducible factor 1-alpha (HIF1α) interferes with angiopoietin-like protein 2 (ANGPTL2) to attenuate high glucose-triggered hypoxia/reoxygenation injury in cardiomyocytes

Abstract

To investigate the role of hypoxia-inducible factor 1-alpha (HIF1A) in hypoxia/reoxygenation (H/R) injury of cardiomyocytes induced by high glucose (HG). The in vitro model of coronary heart disease with diabetes was that H9c2 cells were stimulated by H/R and HG. Quantitative reverse transcription PCR (RT-qPCR) and Western blot analysis were used to detect the expression of HIF1A and angiopoietin-like protein 2 (ANGPTL2) in H9c2 cells. Cell viability and apoptosis were, respectively, estimated by Cell Counting Kit 8 (CCK-8) and TUNEL assays. Lactate dehydrogenase (LDH) activity, inflammation and oxidative stress were in turn detected by their commercial assay kits. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were used to confirm the association between HIF1A and ANGPTL2 promoter. The expression of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway-related proteins and apoptosis-related proteins were also detected by Western blot analysis. As a result, ANGPTL2 expression was upregulated in H9c2 cells induced by HG or/and H/R. ANGPTL2 positively modulated HIF1A expression in H9c2 cells. HG or/and H/R suppressed the cell viability and promoted apoptosis, inflammatory response and oxidative stress levels in H9c2 cells. However, the knockdown of ANGPTL2 could reverse the above phenomena in H/R-stimulated-H9c2 cells through activation of Nrf2/HO-1 pathway. HIF1A transcriptionally activated ANGPTL2 expression. The effect of knockdown of ANGPTL2 on H/R triggered-H9c2 cells was weakened by HIF1A overexpression. In conclusion, knockdown of HIF1A downregulated ANGPTL2 to alleviate H/R injury in HG-induced H9c2 cells by activating the Nrf2/HO-1 pathway.

Effect of empagliflozin on circulating proteomics in heart failure: mechanistic insights into the EMPEROR programme

“… 71 Interestingly, increased levels of ANGPTL2 may also serve as an indicator of increased hypoxic inducible factor 1-α signalling. 62 …”

“…71 Interestingly, increased levels of ANGPTL2 may also serve as an indicator of increased hypoxic inducible factor 1-α signalling. 62 Three prior studies have reported the results of proteomics analyses before and after SGLT2 inhibition, but the three studies each evaluated fewer than 80 patients, <10% of the patients in the current EMPEROR proteomics substudy. 63,72,73 Of the three, the study most comparable to our analyses was carried out by Ferrannini et al, 63 although that study differed from ours in several important respects.…”

Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury

“…These viewpoints align precisely with the results of our bioinformatics analysis. It’s worth noting that there is still a debate over the primary mechanism of “autophagic cell death”, whether it involves excessive mitophagy or the extensive accumulation of autophagosomes [ 65 ]. A new consensus is emerging that the changes induced by cellular damage align with the formation and initiation of autophagosomes in myocardial cells, contributing to the process of cell death [ 66 ].…”

Sp1 transcription factor represses transcription of phosphatase and tensin homolog to aggravate lung injury in mice with type 2 diabetes mellitus-pulmonary tuberculosis

“…The vector was transfected in cells stably transfected with si-SP1. After 48 h, the luciferase activity was determined using the dual luciferase reporter system (Promega) [ 30 ].…”