PTEN/PI3K pathways are involved in the signal transduction of myocardial remodeling in patients with congestive heart failure

Abstract

To investigate the roles of PTEN (phosphatase and tensin homologue deleted on chromosome ten)/PI3K (phosphatidylinositol 3 kinase) signal transduction pathways in myocardium remodeling in patients with congestive heart failure (CHF). A small amount of papillary muscle tissue was collected during mitral valve displacement from 39 patients of mitral valve disease with CHF, 12 cases with grade II, 15 cases with grade III, and 12 cases with grade IV cardiac function. 30 cases of healthy persons and 8 cases of heart donors who died of accident were included as controls. Pathological examination was conducted. Immunoprecitipation was used to assay the protein expression and phosphorylation of PTEN, PI3K and Akt (protein kinase B), and protein expression of alpha-skeletal-actin in myocardial tissues. Typical myocardial remodeling was shown in the myocardial tissues from the valvular heart disease patients with CHF. Hypertrophy was dominant in the myocardial tissues at early stagy of CHF, the myocardial tissues in the end stage of CHF was characterized by disordered alignment of myocytes, discontinuity and dissolving of cardiac fiber, destroyed subcellular organs, and hyperplasia of interstitial tissue. The protein expression of PTEN [absorbance value (A) ratio of PTEN and beta-actin] in control group was 3.29 +/- 0.11, grade II cardiac function was 2.56 +/- 0.19, grade III was 1.52 +/- 0.35, grade IV was 0.91 +/- 0.10, PTEN protein expressions in CHF groups were lower than that of control group and negatively correlated to the levels of cardiac function (P < 0.05 or 0.01). On the contrary, The phosphorylation of PI3K (PI3K/beta-actin) in control group was 0.21 +/- 0.04, grade II cardiac function was 0.52 +/- 0.09, grade III was 1.12 +/- 0.29, grade IV was 1.62 +/- 0.54; The phosphorylation of Akt (Akt/beta-actin) in control group was 0.75 +/- 0.13, grade II cardiac function was 1.21 +/- 0.34, grade III was 2.45 +/- 0.71, grade IV was 3.55 +/- 0.80; The protein expression of alpha-skeletal-actin (alpha-skeletal-actin/beta-actin) in control group was 0.20 +/- 0.03, grade II cardiac function was 0.41 +/- 0.04, grade III was 0.82 +/- 0.09, grade IV was 1.56 +/- 0.11, their expressions in CHF groups were higher than that of control group and positively correlated to the levels of cardiac function (P < 0.05 or 0.01). Both the PTEN and PI3K signal pathways are involved in the pathogenesis of myocardial remodeling in CHF patients with valvular heart disease, which play an important role in the pathogenesis of myocardial hypertrophy. PTEN may play a negative regulation role in the process of myocardial remodeling.