Role of platelet-derived growth factor receptor-mediated signal transduction in myocardial hypertrophy of spontaneously hypertensive rats / 生理学报

ABSTRACT

The role of platelet-derived growth factor (PDGF) receptor-mediated signal transduction in myocardial hypertrophy of spontaneously hypertensive rats (SHR) was investigated. The protein expressions of PDGF beta receptor and extracellular signal-regulated kinase 1/2 (ERK 1/2) and the level of phosphorylated ERK 1/2 (pERK 1/2) in cardiac tissues from 4- and 12-week-old SHR and their age-matched normotensive control Wistar-Kyoto rats (WKY) were examined by Western blot analysis. The results showed that arterial systolic and diastolic blood pressure, +/-dp/dt(max) and the ratio of left ventricular weight to body weight were unchanged in 4-week-old SHR, while they were increased significantly in 12-week-old SHR as compared with those of age-matched WKY. There were no differences in PDGF beta receptor, pERK 1/2, and ERK 1/2 between 4-week-old WKY and SHR. The expression of PDGF beta receptor of 12-week-old SHR was significantly increased by 32.77% (P<0.05) as compared with that of age-matched WKY. Although the expression of ERK 1/2, the downstream signal molecule of PDGF receptor-mediated signal transduction pathway, was unchanged, the level of pERK 1/2, the active form of ERK 1/2, was increased by 19.6% (P=0.01) in 12-week-old SHR. To further elucidate the effect of PDGF beta receptor on cardiomyocyte growth and the relation between PDGF beta receptor and ERK 1/2 activity, (3)H leucine incorporation assay and immunoblotting analysis of pERK 1/2 were performed after cultured neonatal rat cardiomyocytes were stimulated with PDGF-BB. It was shown that (3)H leucine incorporation and pERK 1/2 level were significantly increased after PDGF-BB stimulation. These findings suggest that PDGF beta receptor may play an important role in the myocardial hypertrophy of spontaneously hypertensive rats.