Promotion of PTEN on apoptosis through PI3K/Akt signal in vascular smooth muscle cells of mice model of coronary heart disease.

Previous studies have shown that phosphatase and tensin homolog (PTEN) are key regulators of the development of many malignant tumors and other diseases. However, its regulatory effect on coronary heart disease (CHD) has rarely been reported. Therefore, the regulatory effect of PTEN on the survival and cell death of vascular smooth muscle cells (VSMCs) in CHD mice was elucidated in this study. It was found that the protein and messenger RNA expressions of PTEN in VSMCs of 10 CHD mice were lower than those of normal mice. Then PTEN was overexpressed in VSMCs. It was suggested that the upregulation of PTEN was not conducive to the proliferation and survival of VSMCs in the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assay. The flow cytometry (Annexin V-Fluorescein isothiocyanate (FITC)/propidium iodide) and the terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to detect the apoptotic rate of overexpressing PTEN cells. Some data showed that the expression of PTEN could lead to increased apoptotic rate. It was shown that antiapoptotic Bcl-2 levels were decreased, but cleaved caspase-3 and proapoptotic Bax levels were promoted by SIRT6 overexpression in Western blot analysis. Moreover, PI3K/Akt expression and phosphorylation were significantly decreased in cells expressing PTEN. Recovery of PI3K expression inhibited the suppressive influence of PTEN on VSMC survival, as evidenced by the activated PI3K/Akt pathway, increased cell proliferative rate, reduced the apoptotic level, and reversed expression patterns of Bcl-2 and Bax. Therefore, the findings in this study provide a new idea on the occurrence and development mechanism of CHD and may promote the discovery of innovative therapies.