ABSTRACT
Background: Acute coronary syndrome (ACS) is one of the leading causes of death and is often accompanied by hypertension. Methods: We investigated whether hypertension affects the metabolism of patients with ACS. Serum samples were provided from healthy controls (HCs; n=26), patients with ACS (n=20), or those patients with ACS complicated with hypertension (HTN, n=21), and all were subjected to non-targeted metabolomics analyses based on gas chromatography-mass spectrometry (GC/MS). Differential metabolites were screened using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA). Kyoto Encyclopedia of Genes and Genomes (KEGG) provided metabolic pathways related to these metabolites. Results: Compared to those in the HC group, 12 metabolites were significantly upregulated and 6 significantly downregulated in the ACS group; among these, L-cystine and isocitric acid showed the most obvious differences, respectively. Compared to those in the ACS group, 3 metabolites were significantly upregulated and 2 metabolites were significantly downregulated in the ACS-HTN group, among which oleic acid and chenodeoxycholic acid showed the most marked difference, respectively. The five most prominent metabolic pathways involved in differential metabolites between the ACS and HC groups were arginine biosynthesis; oxidative phosphorylation; alanine, aspartate and glutamate metabolism; citrate cycle; and glucagon signaling pathway. The metabolic pathways between the ACS and ACS-HTN groups were steroid biosynthesis, fatty acid biosynthesis, arginine biosynthesis, primary bile acid biosynthesis, and tyrosine metabolism. Conclusions: A comprehensive study of the changes in circulatory metabolomics and the influence of HTN was conducted in patients with ACS. A serum metabolomics test can be used to identify differentially metabolized molecules and allow the classification of patients with ACS or those complicated with HTN.
ABSTRACT
BACKGROUND: Over the past few decades, numerous clinical and experimental studies have confirmed that oxidative stress is enhanced in heart failure (HF). We recently found that inhibition of highly expressed dynamin2 can protect myocardial ischemia-reperfusion injury in mice and inhibit oxidative stress in ischemic cardiomyocytes. However, the specific mechanisms are still not fully understood. In this study, we hypothesized that oxidative stress induces cardiomyocyte apoptosis through IGF2BP2 regulation, which is regulated through the dynamin2 expression. METHODS: H2O2-treated cardiomyocytes were observed for the regulatory effect of reactive oxygen species (ROS) on IGF2BP2 and the effect of IGF2BP2 on dynamin2 gene expression was determined by lentiviral-mediated IGF2BP2 overexpression. Then, siRNA knockdown of dynamin2 was used to observe whether it can alter the effect of IGF2BP2 on myocardial cells. Finally, IGF2BP2 was knocked down in ischemic rats using shRNA to determine the effects of IGF2BP2 on myocardial ischemia. RESULTS: ROS can promote dynamin2 expression by inducing IGF2BP2 expression and dynamin2 knockdown could reduce the injury of IGF2BP2 to cardiomyocytes. Inhibition of IGF2BP2 expression in myocardial ischemic rats ameliorated cardiac fibrosis in ischemic myocardium. CONCLUSION: Oxidative stress can induce cardiomyocyte apoptosis through the IGF2BP2-dynamin2 pathway. Inhibition of IGF2BP2 expression significantly improves the fibrosis and remodeling that occurs in ischemic myocardium.
