title: [Calpain mediated pulmonary vascular remodeling in hypoxia induced pulmonary hypertension].
abstract: OBJECTIVE
  To explore the role of calpain in pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension and the underlying mechanisms.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided into the hypoxia group and the normoxia control group. Right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored by a method with right external jugular vein cannula. Right ventricular hypertrophy index was presented as the ratio of right ventricular weight to left ventricular weight (left ventricle plus septum weight). Levels of calpain-1, -2 and -4 mRNA in pulmonary artery were determined by real-time PCR. Levels of calpain-1, -2 and -4 protein were determined by Western blot. Primary rat pulmonary arterial smooth muscle cells (PASMCs) were divided into 4 groups: a normoxia control group, a normoxia+MDL28170 group, a hypoxia group and a hypoxia+MDL28170 group. Cell proliferation was detected by MTS and flow cytometry. Levels of Ki-67 and proliferating cell nuclear antigen (PCNA) mRNA were determined by real-time PCR.
  
  
  RESULTS
  RVSP, mPAP and right ventricular remodeling index were significantly elevated in the hypoxia group compared to those in the normoxia group. In the hypoxia group, pulmonary vascular remodeling was significantly developed, accompanied by up-regulation of calpain-1, -2 and -4. MDL28170 significantly inhibited hypoxia-induced proliferation of PASMCs concomitant with the suppression of Ki-67 and PCNA mRNA expression.
  
  
  CONCLUSIONS
  Calpain mediates vascular remodeling via promoting proliferation of PASMCs in hypoxia-induced pulmonary hypertension.
authors.affiliation: Department of Pharmacy, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Weifang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Aizhen
authors.initials: A
authors.lastname: Xiong
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Pharmacy, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Ruilai
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Shegui
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Changping
authors.initials: C
authors.lastname: Hu
mesh_terms: D000818:Animals; D002154:Calpain / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D004151:Dipeptides / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular; D000860:Hypoxia; D019394:Ki-67 Antigen / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects; D011651:Pulmonary Artery; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D066253:Vascular Remodeling / Q000235:genetics* / Q000502:physiology*
chemical_list: D004151:Dipeptides; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D002154:Calpain; C058076:calpain inhibitor III