Cardiopulmonary Bypass Decreases Activation of the Signal Transducer and Activator of Transcription 3 (STAT3) Pathway in Diabetic Human Myocardium.


Journal Article

Cardiopulmonary bypass (CPB) is associated with increased myocardial oxidative stress and apoptosis in diabetic patients. A mechanistic understanding of this relationship could have therapeutic value. To establish a possible mechanism, we compared the activation of the cardioprotective signal transducer and activator of transcription 3 (STAT3) pathway between patients with uncontrolled diabetes (UD) and nondiabetic (ND) patients.Right atrial tissue and serum were collected before and after CPB from 80 patients, 39 ND and 41 UD (HbA1c ≥ 6.5), undergoing cardiac operations. The samples were evaluated with Western blotting, immunohistochemistry, and microarray.On Western blot, leptin levels were significantly increased in ND post-CPB (p < 0.05). Compared with ND, the expression of Janus kinase 2 and phosphorylation (p-) of STAT3 was significantly decreased in UD (p < 0.05). The apoptotic proteins p-Bc12/Bc12 and caspase 3 were significantly increased (p < 0.05), antiapoptotic proteins Mcl-1, Bcl-2, and p-Akt were significantly decreased (p < 0.05) in UD compared with ND. The microarray data suggested significantly increased expression of interleukin-6 R, proapoptotic p-STAT1, caspase 9, and decreased expression of Bc12 and protein inhibitor of activated STAT1 antiapoptotic genes (p = 0.05) in the UD patients. The oxidative stress marker nuclear factor-κB was significantly higher (p < 0.05) in UD patients post-CPB compared with the pre-CPB value, but was decreased, albeit insignificantly, in ND patients post-CPB.Compared with ND, UD myocardium demonstrated attenuation of the cardioprotective STAT3 pathway. Identification of this mechanism offers a possible target for therapeutic modulation.

Full Text

Cited Authors

  • Owais, K; Huang, T; Mahmood, F; Hubbard, J; Saraf, R; Bardia, A; Khabbaz, KR; Li, Y; Bhasin, M; Sabe, AA; Sellke, F; Matyal, R

Published Date

  • November 2015

Published In

Volume / Issue

  • 100 / 5

Start / End Page

  • 1636 - 1645

PubMed ID

  • 26228595

Pubmed Central ID

  • 26228595

Electronic International Standard Serial Number (EISSN)

  • 1552-6259

International Standard Serial Number (ISSN)

  • 0003-4975

Digital Object Identifier (DOI)

  • 10.1016/j.athoracsur.2015.05.013


  • eng