We investigated whether mitogen-activated protein kinases (MAPKs) are changed in the hearts of patients with diabetes after cardioplegia and cardiopulmonary bypass (CP/CPB) operations.
Biopsies from the right atrial appendage were harvested pre- and post-CP/CPB from nondiabetic (ND) patients (n = 8, hemoglobin A1c (HbA1c) = 5.4 ± 0.12); patients with controlled diabetes (CDM) (n = 8, HbA1c = 6.5 ± 0.15); and patients with uncontrolled diabetes (UDM) (n = 8, HbA1c = 9.6 ± 0.3) undergoing coronary artery bypass grafting. The expression and/or activation of the p38-MAPK, ERK1/2, JNK, and MKP-1 in the right-atrial tissues were analyzed by Western blotting. The vasomotor function of coronary arterioles was measured by videomicroscopy.
The post-CP/CPB levels of total p38-MAPK were decreased in the 3 groups as compared with their pre-CP/CPB levels (P < .05). There were increases in phospho-p38-MAPK, phospho-ERK1/2, and MKP-1 in UDM patients as compared with ND and CDM patients at baseline (P < .05). Compared to pre-CP/CPB, the post-CP/CPB levels of phospho-p38-MAPK decreased in the UDM group but were unaltered in the ND and CDM groups; however, the post-CP/CPB levels of phospho-p38-MAPK still remained greater than the post-CP/CPB levels of the other 2 groups. Post-CP/CPB levels of phospho-ERK1/2 were increased in the ND and CDM groups but were decreased in the UDM group compared to their pre-CP/CPB levels, respectively (P < .05). There were no significant differences in phospho-JNK in 3 groups at baseline. Post-CP/CPB levels of phospho-JNK, however, were increased in the 3 groups and were more pronounced in the myocardium of the UDM group (P < .05). After CP/CPB, the protein levels of MKP-1 were unchanged in the 3 groups when compared with their pre-CP/CPB levels. Post-CP/CPB levels of MKP-1, however, remained greater in the UDM group than in the ND and CDM groups. The post-CP/CPB contractile responses to the thromboxane A2 analog U46619 were significantly impaired in all 3 groups compared with pre-CP/CPB contractile responses. These impairments were more pronounced in the UDM group.
Uncontrolled diabetes is associated with changes in expression of and activation of MAPKs and vasomotor dysfunction in the setting of CP/CPB.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Surgery
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale.Physiol Rev. 2010; 90: 1507-1546
- Mitogen-activated protein kinase pathways and cardiac surgery.J Thorac Cardiovasc Surg. 2004; 127: 806-811
- Activation of mitogen-activated protein kinases in human heart during cardiopulmonary bypass.Circ Res. 2000; 12: 1004-1007
- Oscillation in the activities of MEK/ERK1/2 during cardiopulmonary bypass in pigs.Surgery. 2001; 130: 182-191
- Inactivation of the MEK/ERK pathway in the myocardium during cardiopulmonary bypass.J Thorac Cardiovasc Surg. 2001; 121: 773-781
- Activation of pulmonary mitogen-activated protein kinases during cardiopulmonary bypass.J Surg Res. 2003; 115: 56-62
- Mitogen-activated protein kinase inhibition and cardioplegia-cardiopulmonary bypass reduce coronary myogenic tone.Circulation. 2003; 108: II348-II353
- Cardiopulmonary bypass reduces peripheral microvascular contractile function by inhibition of mitogen-activated protein kinase activity.Surgery. 2003; 134: 247-254
- Ischemic preconditioning phosphorylates mitogen-activated kinases and heat shock protein 27 in the diabetic rat heart.Horm Metab Res. 2009; 41: 10-15
- Chronic inhibition of p38MAPK improves cardiac and endothelial function in experimental diabetes mellitus.Eur J Pharmacol. 2007; 554: 40-45
- No correlation between the p38 MAPK pathway and the contractile dysfunction in diabetic cardiomyocytes: hyperglycaemia-induced signaling and contractile function.Pflugers Arch. 2005; 451: 328-337
- Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy.Diabetologia. 2004; 47: 1210-1222
- Inhibition of p38 mitogen-activated protein kinase attenuates left ventricular dysfunction by mediating pro-inflammatory cardiac cytokine levels in a mouse model of diabetes mellitus.Diabetes. 2007; 6: 641-646
- Mitogen-activated protein kinases in the acute diabetic myocardium.Mol Cell Biochem. 2003; 249: 59-65
- Protein kinase C-α modulates microvascular reactivity in the human coronary and skeletal microcirculation.Surgery. 2007; 142: 243-252
- Endothelin-1 induced contractile responses of human coronary arterioles via endothelin-A receptors and PKC-α signaling pathways.Surgery. 2010; 147: 798-804
- Endothelin-1 induced contraction and signaling in the human skeletal muscle microcirculation.Circulation. 2010; 122: S150-S155
- Thromboxane-induced contractile response of human coronary arterioles is diminished post-cardioplegic arrest.Ann Thorac Surg. 2011; 92: 829-836
- Decreased contractile response to endothelin-1 of peripheral microvasculature from diabetic patients.Surgery. 2011; 149: 247-252
- Changes in microvascular reactivity after cardiopulmonary bypass in patients with poorly controlled versus controlled diabetes.Circulation. 2012; 126: S73-S80
- Vasomotor dysfunction after cardiac surgery.Eur J Cardiothorac Surg. 2004; 26: 1002-1014
Accepted: May 10, 2013
Supported in part by National Institutes of Health R01 grants-HL-46716 and HL-69024 (FWS) and NIH training grant 5T32-HL-094300-03 (AAS).
© 2013 Mosby, Inc. Published by Elsevier Inc. All rights reserved.