Effect of Ang II on PDGF receptor expression in vascular smooth muscle cell / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of angiotensin II (Ang II) on platelet-derived growth factor(PDGF) receptor expression in vascular smooth muscle cell(VSMC).</p><p><b>METHODS</b>Restenosis model was established by balloon injury in rat aorta. The morphologic change and level of Ang II were measured at 14th day after operation. The expression of PDGF-beta receptor was detected by Western blot. The cultured VSMC pretreated with or without losartan were treated with Ang II.</p><p><b>RESULTS</b>Compared with sham group, the sections of injured aorta showed marked intimal thickening with large numbers of VSMCs proliferation throughout intima and media, the level of Ang II obviously increased by 78.8% (P < 0.05), the expression of PDGF-beta receptor significantly increased by 83.9% (P < 0.05) at 14th day after operation. The expression of PDGF-beta receptor in cultured VSMC treated with Ang II was higher than that of control group (P < 0.01). The effect of Ang II was inhibited remarkably by pretreatment with losartan.</p><p><b>CONCLUSION</b>Ang II can stimulate PDGF receptor expression in VSMC, it may be an important mechanism of Ang II-induced VSMC proliferation.</p>

Angiotensin II induced upregulation of G alpha q/11, phospholipase C beta 3 and extracellular signal-regulated kinase 1/2 via angiotensin II type 1 receptor / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The role of the G alpha q/11-mediated signal transduction pathway in angiotensin II (AngII) induced cardiac hypertrophy remains unclear. This study was to investigate the role of the G alpha q/11 signal transduction pathway in the development of cardiac hypertrophy in 2K1C hypertensive rats and in cultured neonatal rat ventricular myocytes (NRVMs) and to elucidate the effects of the pathway on AngII induced cardiac hypertrophy.</p><p><b>METHODS</b>Renal hypertension was induced in 2K1C hypertensive rats by placing a silver clip around the left renal artery. At 8 weeks after operation, the systolic blood pressure, the ratio of left ventricular weight to body weight (LV/BW), and the concentration of AngII in the heart were measured. The protein levels of G alpha q/11 and extracellular signal-regulated kinase 1/2 (ERK1/2) were assayed by Western blot analysis, and the activity of phospholipase C (PLC) in the myocardium was detected using [(3)H]-PIP2 as a substrate. Changes in [(3)H]-leucine incorporation and in the protein levels of the signal molecules G alpha q/11, PLC beta 3, and ERK1/2 were measured after NRVMs were stimulated with 10(-7) mol/L AngII.</p><p><b>RESULTS</b>The protein levels of G alpha q/11 and ERK1/2 in the hearts of 2K1C rats increased by 35.8% and 31.9%, respectively, compared with the sham group. The PLC activity in the 2K1C group was also significantly increased (P < 0.05). The levels of G alpha q/11, PLC beta 3, and ERK1/2 increased significantly after NRVMs were stimulated by AngII. The upregulation of G alpha q/11, PLC beta 3 and ERK1/2 in NRVMs occurred prior to [(3)H]-leucine incorporation increases, and could be inhibited with losartan.</p><p><b>CONCLUSION</b>AngII can initiate cardiac hypertrophy and upregulate signal molecules in the G alpha q/11-mediated signal transduction pathway, such as G alpha q/11, PLC beta 3 and ERK1/2, at both tissue and cellular levels.</p>

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

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.