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

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Presentation on theme: "Cardiopulmonary Bypass Decreases Activation of the Signal Transducer and Activator of Transcription 3 (STAT3) Pathway in Diabetic Human Myocardium  Khurram."— Presentation transcript:

1 Cardiopulmonary Bypass Decreases Activation of the Signal Transducer and Activator of Transcription 3 (STAT3) Pathway in Diabetic Human Myocardium  Khurram Owais, MD, Thomas Huang, BA, Feroze Mahmood, MD, Jeffery Hubbard, MD, Rabya Saraf, BA, Amit Bardia, MD, Kamal R. Khabbaz, MD, Yunping Li, MD, Manoj Bhasin, PhD, Ashraf A. Sabe, MD, Frank Sellke, MD, Robina Matyal, MD  The Annals of Thoracic Surgery  Volume 100, Issue 5, Pages (November 2015) DOI: /j.athoracsur Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 Representative hemotoxylin and 3,3′-diaminobenzidine immunohistochemical staining for phosphorylated leptin receptors (p-Ob-R) at original magnification ×20 in (A, B) nondiabetic and (C, D) uncontrolled diabetic patients before and after cardiopulmonary bypass (CPB). (E) Quantitative analysis of leptin showed similar baseline values in nondiabetic and uncontrolled diabetic patients. However, nondiabetic tissue exhibited greater increase in p-Ob-R staining post-cardiopulmonary bypass. Data are expressed as mean ± standard deviation. *p < 0.05 vs ND pre- CPB. (CP = cardioplegic arrest.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 Representative hematoxylin and 3,3′-diaminobenzidine immunohistochemical staining for interleukin-6 (IL-6)-positive cells. Qualitative analysis showing similar baseline values in the (A) nondiabetic (ND) group and in the (C) uncontrolled diabetic (UD) group; but (B) ND patients post-CPB had increased p-Ob-R stained cells compared with (D) UD patients post-CPB. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 Janus kinase (JAK)/signal transducer and activator of transcription (STAT) quantitative analysis of immunoblotting for key proteins involved in the pathway: (A) JAK2, (B) suppressor of cytokine signaling 3 (SOCS3), (C) phosphorylated (p)-STAT3/STAT3, (D) p-STAT5/STAT5, and (E) p-STAT1/STAT1. Data are expressed as mean ± standard deviation. *p < 0.05 vs ND pre-CPB, Øp < 0.05 vs UD pre-CPB, †p < 0.05 vs ND post-CPB. (F) Immunoblots. (CPB = cardiopulmonary bypass; ND = nondiabetic; UD = uncontrolled diabetic.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 Representative human atrial tissue immunoblots and quantitative analysis of proapoptotic and antiapoptotic proteins (A) phosphorylated (p)Bcl2/Bcl2, (B) caspase 3, (C) Bcl2, (D) pAkt (protein kinase B), (E), Mcl2, and (F) Bck-xl. Data are expressed as the mean ± standard deviation. *p < 0.05 vs ND pre-CPB, Øp < 0.05 vs UD pre-CPB, ¶p < 0.05 vs ND pre-CPB, †p < 0.05 vs ND post-CPB. (CP = cardioplegia; CPB = cardiopulmonary bypass; GAPDH = glyceraldehyde-3-phosphate dehydrogenase; ND = nondiabetic; UD = uncontrolled diabetic.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

6 Fig 5 Representative immunoblotting and quantitative analysis of human atrial tissue for oxidative stress and neurogenesis: (A) nuclear factor-κB (NF-κB) and (B) manganese-containing superoxide dismutase (MnSOD). Data are expressed as the mean ± standard deviation. *p < 0.05 vs ND pre-CPB, Øp < 0.05 vs UD pre-CPB, ¶p < 0.05 vs ND pre-CPB CD, †p < 0.05 vs ND post-CPB. (CPB = cardiopulmonary bypass; ND = nondiabetic; UD = uncontrolled diabetic.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

7 Fig 6 Proposed cardioprotective pathway of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway in patients with uncontrolled diabetes (UD). Levels of JAK2 were decreased and suppressor of cytokine signaling 3 (SOCS3) was elevated. Increased activation of STAT1 led to increased apoptosis. In UD patients, decreased phosphorylated STAT3 resulted in diminished cardioprotection of the myocardium. UD patients displayed decreased antiapoptosis as well as increased oxidative stress and decreased neurogenesis at the gene, protein, and cellular levels. (IL-6 = interleukin 6; MnSOD = manganese-containing superoxide dismutase; NF-κB = nuclear factor-κB.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

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