Background
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.
Methods
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.
Results
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.
Conclusion
Uncontrolled diabetes is associated with changes in expression of and activation of
MAPKs and vasomotor dysfunction in the setting of CP/CPB.
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Article info
Publication history
Accepted:
May 10,
2013
Footnotes
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).
Identification
Copyright
© 2013 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
