[The influence of inhibiting notch signal on pulmonary vascular remodeling induced by PDGF].

Objective: To explore the influence of inhibiting Notch signal on pulmonary vascular remodeling induced by PDGF.

Methods: Vessel strips taken from healthy Wistar rats were cultured together with extrogenous PDGF, the potent smooth muscle cell proliferation stimulators, for 7 days. Some vessel strips were cultured with PDGF and gamma-secretase inhibitor DAPT, a Notch signaling inhibitor for 7 days. Vascular wall thickness, PCNA and caspase-3 positive cell rate were examined in vessel strips. The alterations of Notch 1 to 4 receptor and HERP1, 2 mRNA were discerned by FQ-PCR to observe the influence of DAPT on Notch signal. At the same time, above indexes, which were related with pulmonary vascular remodeling, were measured too.

Results: PDGF stimulation in the cultured normal pulmonary arteries resulted in vascular medial thickness increase for about 50%, accompanied by significant increase in PCNA positive cell rate and decrease of caspase-3 positive cell rate. When DAPT were added to inhibit Notch signaling, the expression of HERP1, 2 mRNA decreased, the degrees of PDGF induced vascular medial thickness and PCNA positive cell rate increase as well as caspase-3 positive cell rate decrease were all attenuated notably.

Conclusion: Inhibiting Notch signal induced by gamma-secretase inhibitor lead to the suppression of pulmonary vascular remodeling induced by PDGF, suggesting inhibition of Notch signal pathway might be a novel strategy in the intervention of pulmonary hypertension.