title: Role of notch signal in angiotensin II induced pulmonary vascular remodeling.
abstract: OBJECTIVE
  Notch signal is particularly important to vascular remodeling during the process of embryonic development, vessel repair and tumor growth, but there are few studies about pulmonary vascular remodeling in pulmonary hypertension. This study was to explore the effect of inhibiting Notch signal on pulmonary vascular remodeling induced by angiotensin II.
  
  
  METHODS
  Vessel strips taken from healthy Wistar rats were cocultured with extrogenous angiotensin II and the potent smooth muscle cell proliferation stimulators for 7 days. Vascular wall thickness, proliferating cell nuclear antigen (PCNA) positive cell rate, and caspase-3 positive cell rate were examined in vessel strips. Some of the vessel strips were cultured with angiotensin II and γ-secretase inhibitor DAPT, a Notch signaling inhibitor, for 7 days. The levels of Notch 1 to 4 receptor and HERP1/2 mRNA were ascertained by FQ-PCR.
  
  
  RESULTS
  Angiotensin II stimulation in the cultured normal pulmonary arteries resulted in an increase in the vascular medial thickness by nearly 50%, and a significant increase in the PCNA positive cell rate and a decrease in the caspase-3 positive cell rate (P<0.05). DAPT treatment did not alter the levels of Notch 1 to 4 receptor but remarkably decreased HERP1 and HERP2 mRNA expression (P<0.05). DAPT treatment also decreased angiotensin II-induced vascular medial thickness and PCNA positive cell rate, and increased caspase-3 positive cell rate (P<0.05).
  
  
  CONCLUSIONS
  Inhibition of Notch signal by the γ-secretase inhibitor may suppress pulmonary vascular remodeling induced by angiotensin II, suggesting that the inhibition of Notch signal pathway might be a novel strategy for the treatment of pulmonary hypertension.
authors.affiliation: Department of Pediatrics, Second West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Qiao
authors.affiliation: Department of Pediatrics, Second West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, Second West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Shi
authors.affiliation: Department of Pediatrics, Second West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Tong-Fu
authors.initials: TF
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, Second West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Hua
authors.affiliation: Department of Pediatrics, Second West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Han-Min
authors.initials: HM
authors.lastname: Liu
keywords: Notch signal; angiotensin; lung; rat; vascular remodeling
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