Background: Heat shock protein 90 (HSP90) appears to have a pivotal function in ischemic preconditioning. Pioglitazone preconditioning (PioC) attenuates myocardial ischemia/reperfusion (I/R) injuries.
Objectives: The current study aims to investigate the role of HSP90, complement C3 and C5a, and nuclear factor kappa-B (NF-κB) in PioC-induced cardioprotection.
Material and methods: A total of 80 rats were randomly categorized into 4 groups, as follows: sham, I/R, PioC, and PioC+HSP90 inhibitor geldanamycin (PioC+GA). The sham group rats had a thoracotomy, in which the ligature was passed by the heart with no ligation (150 min). The other 3 groups were exposed to ischemia (30 min) followed by reperfusion (2 h). In the PioC group, pioglitazone (3 mg/kg) was administered intravenously 24 h before ischemia. In the PioC+GA group, after being pretreated with pioglitazone, GA was administered (intraperitoneally, 1 mg/kg) 30 min before ischemia. Myocardial infarct sizes (ISs), apoptosis rates, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin I (cTnI) serum levels were determined. The HSP90, C3, NF-κB, C5a, B-cell lymphoma-2 (Bcl-2), and Bax expression levels, as well as interleukin (IL)-1β, IL-6, intercellular cell adhesion molecule-1 (ICAM-1), and tumor necrosis factor alpha (TNF-α) mRNA levels were measured.
Results: The myocardial ISs, serum CK-MB, cTnI and LDH levels, apoptosis rates, IL-1β, IL-6, TNF-α, ICAM-1 release, as well as Bax, C5a, C3, and NF-κB protein expression were considerably lower in the PioC group than in the I/R group (p < 0.05). The Bcl-2 and HSP90 expression was higher in the PioC group than in the I/R group (p < 0.05). Geldanamycin inhibited the effects of PioC. These data strongly demonstrate that the PioC-induced is dependent upon HSP90 activity.
Conclusions: The HSP90 is indispensable for PioC-mediated cardioprotection. The HSP90 attenuates I/R-induced ISs, apoptosis of cardiomyocytes and myocardial inflammation through C3, C5a and NF-κB activation inhibition.
Keywords: C3; C5a; HSP90; NF-κB; pioglitazone preconditioning.