TY - JOUR
T1 - Decreased PGC-1α Post-Cardiopulmonary Bypass Leads to Impaired Oxidative Stress in Diabetic Patients
AU - Mahmood, Eitezaz
AU - Jeganathan, Jelliffe
AU - Feng, Ruby
AU - Saraf, Maria
AU - Khabbaz, Kamal
AU - Mahmood, Faraz
AU - Venkatachalam, Senthilnathan
AU - Liu, David
AU - Chu, Louis
AU - Parikh, Samir M.
AU - Matyal, Robina
N1 - Funding Information:
Dr Parikh is listed as an inventor on patent filings by Beth Israel Deaconess Medical Center pertaining to PGC-1α. Dr Robina Matyal is supported by the Department of Anesthesia, Critical Care, and Pain Medicine , Beth Israel Deaconess Medical Center .
Funding Information:
Dr Parikh is listed as an inventor on patent filings by Beth Israel Deaconess Medical Center pertaining to PGC-1α. Dr Robina Matyal is supported by the Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center.
Publisher Copyright:
© 2019 The Society of Thoracic Surgeons
PY - 2019/2
Y1 - 2019/2
N2 - Background: The mechanism of mitochondrial dysfunction after cardiopulmonary bypass (CPB) in patients with diabetes mellitus lacks understanding. We hypothesized that impaired beta-oxidation of fatty acids leads to worsened stress response in this patient population after cardiac surgery. Methods: After Institutional Review Board approval, right atrial tissue samples were collected from 35 diabetic patients and 33 nondiabetic patients before and after CPB. Patients with glycated hemoglobin of 6.0 or greater and a clinical diagnosis of diabetes mellitus were considered to be diabetic. Immunoblotting and microarray analysis were performed to assess protein and gene expression changes. Blots were quantified with ImageJ and analyzed using one-way analysis of variance with multiple Student's t test comparisons after normalization. All p values less than 0.05 were considered significant. Immunohistochemistry was performed for cellular lipid deposition assessment. Results: Diabetic patients had significantly lower levels of PGC-1α before and after CPB (p < 0.01 for both) compared with nondiabetic patients. Several upstream regulators of PGC-1α (SIRT1 and CREB) were significantly higher in nondiabetic patients before CPB (p = 0.01 and 0.0018, respectively). Antioxidant markers (NOX4 and GPX4), angiogenic factors (TGF-β, NT3, and Ang1), and the antiapoptotic factor BCL-xL were significantly lower in diabetic patients after CPB (p < 0.05). The expression of genes supporting mitochondrial energy production (CREB5 and SLC25A40) and angiogenic genes (p < 0.05) was significantly downregulated in diabetic patients after CPB. Immunohistochemistry results showed significantly increased lipid deposition in diabetic myocardial tissue. Conclusions: Decreased PGC-1α in diabetic patients may lead to impaired mitochondrial function and attenuated antiapoptotic and angiogenic responses after CPB. Therefore, PGC-1α and upstream regulators could serve as a target for improving beta-oxidation in diabetic patients.
AB - Background: The mechanism of mitochondrial dysfunction after cardiopulmonary bypass (CPB) in patients with diabetes mellitus lacks understanding. We hypothesized that impaired beta-oxidation of fatty acids leads to worsened stress response in this patient population after cardiac surgery. Methods: After Institutional Review Board approval, right atrial tissue samples were collected from 35 diabetic patients and 33 nondiabetic patients before and after CPB. Patients with glycated hemoglobin of 6.0 or greater and a clinical diagnosis of diabetes mellitus were considered to be diabetic. Immunoblotting and microarray analysis were performed to assess protein and gene expression changes. Blots were quantified with ImageJ and analyzed using one-way analysis of variance with multiple Student's t test comparisons after normalization. All p values less than 0.05 were considered significant. Immunohistochemistry was performed for cellular lipid deposition assessment. Results: Diabetic patients had significantly lower levels of PGC-1α before and after CPB (p < 0.01 for both) compared with nondiabetic patients. Several upstream regulators of PGC-1α (SIRT1 and CREB) were significantly higher in nondiabetic patients before CPB (p = 0.01 and 0.0018, respectively). Antioxidant markers (NOX4 and GPX4), angiogenic factors (TGF-β, NT3, and Ang1), and the antiapoptotic factor BCL-xL were significantly lower in diabetic patients after CPB (p < 0.05). The expression of genes supporting mitochondrial energy production (CREB5 and SLC25A40) and angiogenic genes (p < 0.05) was significantly downregulated in diabetic patients after CPB. Immunohistochemistry results showed significantly increased lipid deposition in diabetic myocardial tissue. Conclusions: Decreased PGC-1α in diabetic patients may lead to impaired mitochondrial function and attenuated antiapoptotic and angiogenic responses after CPB. Therefore, PGC-1α and upstream regulators could serve as a target for improving beta-oxidation in diabetic patients.
UR - http://www.scopus.com/inward/record.url?scp=85058422741&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058422741&partnerID=8YFLogxK
U2 - 10.1016/j.athoracsur.2018.08.009
DO - 10.1016/j.athoracsur.2018.08.009
M3 - Article
C2 - 30291832
AN - SCOPUS:85058422741
SN - 0003-4975
VL - 107
SP - 467
EP - 476
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 2
ER -