Correlation between platelet-derived growth factor signaling pathway and inflammation in desoxycorticosterone-induced salt-sensitive hypertensive rats with myocardial fibrosis.
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.


CONCLUSIONS
In DOCA/salt induced hypertensive rats with MF, excessive activation of PDGF/PDGFR signaling pathway is involved in myocardial inflammation.
Department of Cardiology, Affiliated Provincial Hospital, Anhui Medical University Hefei 230001, China.
Bin
B
Fan
Likun
L
Ma
Qian
Q
Li
Lin
L
Wang
Junling
J
Zhou
Jiawei
J
Wu
D000818:Animals; D001794:Blood Pressure; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D005355:Fibrosis; D006973:Hypertension / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009205:Myocarditis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D017673:Sodium Chloride, Dietary
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta
Desoxycorticosterone; fasudil; inflammatory response; platelet-derived growth factor; platelet-derived growth factor receptor