This study aimed to investigate the role of PDGF/PDGFR signaling pathway in myocardial
fibrosis of
desoxycorticosterone (
DOCA) induced
salt-sensitive hypertensive rats and explore the influence of PDGF/PDGFR signaling pathway on fibroblasts and myofibroblasts in the heart. 60 male SD rats underwent right
nephrectomy and bred with 1%
sodium chloride and 0.1%
potassium chloride for 4 weeks, and then randomly divided into 3 groups (CON group,
DOCA group and DOCA+IMA group). Results showed that: 1) 14 and 28 days after intervention, the SBP in
DOCA and DOCA+IMA group was significantly higher than that in CON group. At days 28, the severity of myocardial
fibrosis and PVCA/VA ratio in
DOCA group were significantly increased when compared with CON group. The severity of myocardial
fibrosis and PVCA/VA ratio in DOCA+IMA group were markedly lower than those in
DOCA group although they were higher than those in CON group. 2) At days 14, the
mRNA expressions of PDGFRα and PDGFRβ in
DOCA group were significantly higher than CON and DOCA+IMA group. At days 28, the
mRNA expressions of PDGFRβ, FSP-1, α-SMA,
procollagen I and
procollagen III in
DOCA group were significantly higher than those in CON group. In addition, in a specific group, the PDGFRβ
mRNA expression was higher than the PDGFRα
mRNA expression. In DOCA+IMA group, the
mRNA expressions of PDGFRβ, FSP-1, α-SMA,
procollagen I and
procollagen III were markedly reduced when compared with
DOCA group. 3) At 14 days, the
protein expressions of PDGFRα and PDGFRβ in
DOCA group were significantly higher than those in CON group. The PDGFRα
protein expression in DOCA+IMA group was markedly lower than that in
DOCA group. At days 28, the
protein expressions of PDGFRα and PDGFRβ in
DOCA group were significantly increased when compared with CON group. The
protein expressions of PDGFRα and PDGFRβ in DOCA+IMA group were significantly lower than those in
DOCA group. At day 28, the cardiac interstitium mainly contained
vimentin positive fibroblasts, and α-SMA positive cells were less identified in CON group. In
DOCA group, α-SMA positive fibroblasts (spindle-shaped) increased significantly, but the myofibroblasts reduced significantly in DOCA+IMA group when compared with
DOCA group. 4) PDGFRα
protein expression was observed in fibroblasts and myofibroblasts, but not in VSMCs. PDGFRβ
protein expression was noted in not only fibroblasts and myofibroblasts but also VSMCs. Thus, During myocardial
fibrosis of
DOCA induced
salt-sensitive hypertensive rats, PDGFRα acts at early stage, but PDGFRβ functions in the whole process. PDGFRα and PDGFRβ expressions increase in fibroblasts and myofibroblasts, suggesting that PDGF/PDGFR signaling pathway is involved in the myocardial
fibrosis via stimulating fibroblasts to proliferate and transform into myofibroblasts.