OBJECTIVE To explore the role of calpain in in pulmonary vascular remodeling in hypoxia induced pulmonary hypertension and the underlying mechanism.METHODS Sprague-Dawley rats were randomly divided into hypoxia group and normoxia control group.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(m PAP)were monitored by the method of right external jugular vein cannula.Right ventricular hypertrophy index was expressed as the ratio of right ventricular weight to left ventricular weight(left ventricle plus septum weight).Level of calpain-1,calpain-2and calpain-4 m RNA in pulmonary artery trunk were determined by real-time PCR.Expression of calpain-1,calpain-2 and calpain-4 protein was determined by Western Blot.Primary rat pulmonary arterial smooth muscle cells(PASMCs)were divided into 4 groups:normoxia control group,normoxia+MDL28170 group,hypoxia group and hypoxia+MDL28170 group.Cell proliferation was detected by MTS and flow cytometry.Level of Ki-67 and PCNA m RNA were determined by real-time PCR.RESULTS RVSP,m PAP and right ventricular remodeling index were significantly higher in the hypoxia group than those in the normoxia group.In the hypoxia group,pulmonary vascular remodeling occurred,and the expression of calpain-1,calpain-2 and calpain-4 m RNA and protein expression was increased in the pulmonary artery.MDL28170 significantly inhibited hypoxia-induced proliferation of PASMCs accompanied with decreased Ki-67and PCNA m RNA expression.CONCLUSION Calpain mediated vascular remodeling via promoting proliferation of PASMCs in hypoxia induced pulmonary hypertension.
