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Int J Clin Exp Pathol 2013;6(11):2468-2475
Correlation between platelet-derived growth factor signaling pathway and inflammation
in desoxycorticosterone-induced salt-sensitive hypertensive rats with myocardial
Bin Fan, Likun Ma, Qian Li, Lin Wang, Junling Zhou, Jiawei Wu
Department of Cardiology, Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China
Received August 16, 2013; Accepted September 21, 2013; Epub October 15, 2013; Published November 1, 2013
Abstract: Objective: To investigate whether inflammation could excessively activate platelet-derived growth factor (PDGF) signaling pathway in
desoxycorticosterone (DOCA) induced salt-sensitive hypertensive rats with myocardial fibrosis (MF). Methods: A total of 30 male SD rats
underwent right nephrectomy and then bred with 1% sodium chloride and 0.1% potassium chloride for 2 weeks. These animals were randomly
divided into 3 groups: CON group, DOCA group and DOCA+FAS group. Systolic blood pressure (SBP) was measured once every 2 weeks; HE
staining was done to observe myocardial inflammation; immunohistochemistry was done to detect expressions of monocyte-macrophage
antigen (ectodermal dysplasia 1, ED-1), PDGFRα and PDGFRβ in the myocardium; real time fluorescence quantitative PCR was employed to
detect the mRNA expressions of DGF-A, PDGF-B, PDGF-C, PDGF-D, PDGFRα and PDGFRβ. Results: The SBP in DOCA group and DOCA+FAS
group increased markedly when compared with CON group (P<0.01), but there was no marked difference between DOCA group and
DOCA+FAS group (P>0.05). At 14 days, in DOCA group, the myocardial inflammation was obvious, ED-1 expression increased markedly, the
mRNA expressions of PDGF-A, PDGF-B, PDGF-C, PDGFRα and PDGFRβ increased to different extents, protein expressions of PDGFRα and
PDGFRβ also elevated markedly (P<0.01), but the PDGF-D mRNA expression remained unchanged, when compared with CON group. After
treatment with fasudil (a drug with anti-inflammatory activity), myocardial inflammation was significantly attenuated, mRNA expressions of
PDGF-A, PDGF-B, PDGF-C and PDGFRα as well as PDGFRα protein expression reduced dramatically (P<0.01), but the mRNA and protein
expressions of PDGFRβ remained unchanged (P>0.05) when compared with DOCA group. Conclusion: In DOCA/salt induced hypertensive
rats with MF, excessive activation of PDGF/PDGFR signaling pathway is involved in myocardial inflammation. (IJCEP1308044).
Keywords: Desoxycorticosterone, platelet-derived growth factor, platelet-derived growth factor receptor, fasudil, inflammatory response
Address correspondence to: Likun Ma, Department of Cardiology, Affiliated Provincial Hospital, Anhui Medical University, Hefei 230001, China.