Effects of Aster B-mediated intracellular accumulation of cholesterol on inflammatory process and myocardial cells in acute myocardial infarction

To investigate the effect of cholesterol accumulation in cells on the inflammatory process of acute myocardial infarction and cardiomyocytes and its mechanism.Blood samples of 15 patients with myocardial infarction were clinically collected to detect enzyme levels of cholesterol and related myocardial parameters in the serum. Correlation analysis was carried out. At the cellular level, simulation of cholesterol entry and exit from cells was conducted by a liposome-loaded cholesterol model in this study, and BNP and inflammatory factors were detected with enzyme-linked immunosorbent assay. Moreover, to investigate the molecular mechanism of myocardial damage caused by cholesterol, Gramd1b and Prkaca of HL-1 were knocked down with small interference RNA technique. Then, inhibitor C3 was used to weaken RhoA activity to explore the level of cardiac muscle cell BNP in order to identify key protein target sites that may be involved in the process of cholesterol damage to cardiac muscle cells.Serum cholesterol concentration showed a significantly positive correlation with the levels of AST, CK, and LD in serum of patients with myocardial infarction. Cholesterol accumulation in cardiac muscle cells significantly increased the levels of BNP, inflammatory factors (IL-1β, IL-6, TNF-α, and CCL-2) in cardiac muscle cells, which exacerbated cardiomyocyte damage. Conversely, cholesterol excretion caused significant downregulation of BNP and inflammatory factors. Moreover, after knocking down Gramd1b, the accumulation of cholesterol in myocardial cells decreased, the levels of BNP and inflammatory factors significantly reduced, and the degree of myocardial cell damage was weakened. Knockdown of Prkaca inhibited RhoA activity and reversed cholesterol-induced elevation of BNP and inflammatory factors.ASTER B-mediated intracellular accumulation of cholesterol in cardiac muscle cells may cause cardiomyocyte damage and inflammatory factor infiltration through PKA-Ca2+-RhoA pathways.