J Cardiovasc Pharmacol Ther . 2016 Sep;21(5):471-7. doi: 10.1177/1074248415624158. Epub 2016 Feb 4.

The PTEN/Akt Signaling Pathway Mediates Myocardial Apoptosis in Swine After Coronary Microembolization

Jiangyou Wang  1 Han Chen  2 Qiang Su  1 You Zhou  1 Tao Liu  1 Lang Li  3

Affiliations

  • 1 Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • 2 Department of Cardiac Surgery, Wuhan Asia Heart Hospital in China, Wuhan, China.
  • 3 Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China drlilang@163.com.

Abstract

Background/aims: Phosphatase and the tensin homolog deleted on chromosome ten (PTEN) has been recognized as a promoter of apoptosis in various tissues and has been shown to be upregulated in circumstances of coronary microembolization (CME). We hypothesized that the upregulation of PTEN correlates with CME-induced myocardial apoptosis.

Methods: Swine CME was induced by an intracoronary injection of inert plastic microspheres (diameter of 42 μm) into the left anterior descending coronary, with or without pretreatment of the PTEN small-interfering RNA (siRNA). Echocardiological measurements, a pathological examination, Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining, and Western blotting, were performed to assess their functional, morphological, and molecular effects in CME.

Results: PTEN was aberrantly upregulated in cardiomyocytes following CME. Downregulation of PTEN in vivo via siRNA was associated with improved cardiac function and attenuated myocardial apoptosis; concomitantly inhibited the expression of key proapoptotic proteins, such as phosphorylated Bad (p-Bad); cleaved caspase-3; and enhanced the expression of key antiapoptotic proteins, such as phosphorylated protein kinase B (p-Akt). However, there was no difference in the Akt-regulated downstream protein IκB kinases (IKKα, IKKβ, and IKKγ) among the sham, CME, and control siRNA groups.

Conclusion: This study demonstrates, for the first time, that the PTEN/Akt signaling pathway contributes to cardiomyocyte apoptosis. The data generated from this study provide a rationale for the development of PTEN-based therapeutic strategies for CME-induced myocardial injury.

Keywords: Akt; Bad; PTEN; apoptosis; caspase-3; coronary microembolization.

0