title: [Effect of inhibition of Notch signal on pulmonary vascular remodeling induced by angiotensin Ⅱ].
abstract: OBJECTIVE
  It is known that Notch signal is very 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 co-cultured 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. Then some 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. DAPT treatment did not result in the alterations of Notch 1 to 4 receptor levels, but decreased remarkably HERP1 and HERP2 mRNA expression. DAPT treatment also decreased angiotensin II-induced vascular medial thickness and PCNA positive cell rate and increased caspase-3 positive cell rate.
  
  
  CONCLUSIONS
  Inhibiting Notch signal by γ-secretase inhibitor may lead to the suppression of 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. iaqiao@163.com
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Qiao
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Xu
authors.forename: Kun
authors.initials: K
authors.lastname: Shi
authors.forename: Tong-Fu
authors.initials: TF
authors.lastname: Zhou
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Hua
authors.forename: Han-Min
authors.initials: HM
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004151:Dipeptides / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D018809:Proliferating Cell Nuclear Antigen; D051880:Receptors, Notch; D000804:Angiotensin II