1. Imatinib attenuates myocardial fibrosis in association with inhibition of the PDGFRα activity.
- Author
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Ma LK, Li Q, He LF, Hua JS, Zhou JL, Yu H, Feng KF, Chen HW, Hu H, and Wang L
- Subjects
- Animals, Benzamides therapeutic use, Blood Pressure drug effects, Blotting, Western, Desoxycorticosterone, Disease Models, Animal, Endomyocardial Fibrosis pathology, Fibronectins analysis, Fibronectins metabolism, Fibrosis drug therapy, Fibrosis pathology, Hypertension chemically induced, Hypertension physiopathology, Imatinib Mesylate, Male, Nephrectomy methods, Piperazines therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Rats, Rats, Sprague-Dawley, Receptor, Platelet-Derived Growth Factor alpha metabolism, Receptor, Platelet-Derived Growth Factor beta antagonists & inhibitors, Receptor, Platelet-Derived Growth Factor beta metabolism, Tenascin analysis, Tenascin metabolism, Treatment Outcome, Benzamides pharmacology, Endomyocardial Fibrosis drug therapy, Piperazines pharmacology, Protein Kinase Inhibitors pharmacology, Pyrimidines pharmacology, Receptor, Platelet-Derived Growth Factor alpha antagonists & inhibitors
- Abstract
Background: Imatinib is a tyrosine kinase receptor inhibitor that has been confirmed to exert inhibitory effect on the platelet derived growth factor PDGF receptor (PDGFRα and PDGFRβ) activity., Objective: To investigate the protective effect of imatinib on the myocardial fibrosis in deoxycorticosterone-acetate (DOCA)/salt induced hypertensive rats., Methods: Sixty male uninephrectomized Sprague-Dawley rats were assigned to three groups: control rats (CON group); deoxycorticosterone group (DOCA group); deoxycorticosterone and imatinib group (DOCA+IMA group). Systolic blood pressure (SBP) was measured biweekly. The apical portion of the left ventricle was studied. Sirius-Red staining, Hematoxylin-Eosin staining, immunohistochemistry and Western blot assay were employed., Results: SBP in the DOCA group and DOCA+IMA group was higher than that in the CON group on day 14 and 28. Animals in the DOCA group showed severe interstitial and perivascular fibrosis on day 28, and the expressions of PI, PIII, tenascin-C and fibronectin were significantly higher than those in the DOCA+IMA group and CON group. When compared with the CON group, myocardial tissue inflammatory response and monocyte/macrophage infiltration of different degrees were observed in the DOCA group and DOCA+IMA group. Protein expressions of PDGF-A, PDGF-C and PDGFRα were significantly higher in the DOCA and DOCA+IMA groups than those in the CON group, but the p-PDGFRα protein expression in the DOCA+IMA group was lower than that in the DOCA group., Conclusion: Imatinib can exert inhibitory effects on myocardial fibrosis in DOCA/salt induced hypertensive rats, which may be attributed to the inhibition of PDGFR-α activity.
- Published
- 2012
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