title: Imatinib attenuates myocardial fibrosis in association with inhibition of the PDGFRα activity.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Anhui Provincial Hospital, Hefei, China. docma96@sina.com
authors.forename: Li-Kun
authors.initials: LK
authors.lastname: Ma
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Li-feng
authors.initials: LF
authors.lastname: He
authors.forename: Jin-sheng
authors.initials: JS
authors.lastname: Hua
authors.forename: Jun-ling
authors.initials: JL
authors.lastname: Zhou
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.forename: Ke-fu
authors.initials: KF
authors.lastname: Feng
authors.forename: Hong-wu
authors.initials: HW
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D004719:Endomyocardial Fibrosis / Q000188:drug therapy* / Q000473:pathology; D005353:Fibronectins / Q000032:analysis / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D000068877:Imatinib Mesylate; D008297:Male; D009392:Nephrectomy / Q000379:methods; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D019063:Tenascin / Q000032:analysis / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D005353:Fibronectins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D019063:Tenascin; D003900:Desoxycorticosterone; D000068877:Imatinib Mesylate; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta