title: Hydroxysafflor yellow A (HSYA) attenuates hypoxic pulmonary arterial remodelling and reverses right ventricular hypertrophy in rats.
abstract: BACKGROUND
  Carthamus tinctorius L. is a traditional herbal medicine native to China with properties of promoting blood circulation and removing blood stasis, which is used for the treatment of cerebrovascular and cardiovascular diseases. Hydroxysafflor yellow A (HSYA) is the main constituent isolated from the flower of Carthamus tinctorius L. which is used as a marker substance in the quality control of Carthamus tinctorius L. in Chinese Pharmacopeia.
  
  
  OBJECTIVE
  This study is to investigate the hypertension attenuating effect of HSYA on hypoxia-induced pulmonary artery hypertension model rats, and the possible mechanism.
  
  
  METHODS
  The animal models were made by treating adult male Wistar rats (of the same age with the same weight of 200±25g) under hypoxia 24h per day for 9 days with or without administration of HSYA. The pulmonary arterial pressure of rats was measured after anesthetization; The right ventricular hypotrophy was evaluated by the right ventricular hypotrophy index (RVHI=[RV/(LV+S)]) as well as histomorphology assay with Hematoxylin and Eosin (HE) staining; The reducing of pulmonary artery remodelling was evaluated by histomorphology assay with HE staining; The proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by immunohistochemistry assays (PCNA and Ki67) and MTT assay. Cell cycle analysis and Weston-blot analysis were also performed in the study.
  
  
  RESULTS
  HSYA reduced the mean right ventricular systolic pressure (RVSP) of rats with hypoxic pulmonary arterial hypertension (HPH) in a manner of concentration dependency. It significantly inhibited the PASMCs proliferation and attenuated the remodelling of the pulmonary artery and right ventricular hypertrophy.
  
  
  CONCLUSIONS
  These findings suggested that HSYA protected against hypoxic induced pulmonary hypertension by reversing the remodelling of the pulmonary artery through inhibiting the proliferation and hypertrophy of PASMCs. This is in accordance with our previous finding that HSYA protects against the pulmonary artery vascular constriction. All these results suggest that HSYA may be a promising candidate for HPH treatment.
authors.affiliation: College of Pharmacy, Harbin Medical University, Daqing 163319, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: The fifth affiliated Hospital of Harbin Medical University, Daqing 163316, China.
authors.forename: Pengda
authors.initials: P
authors.lastname: Dong
authors.affiliation: The fifth Hospital of Daqing City, Daqing 163711, China.
authors.forename: Congjia
authors.initials: C
authors.lastname: Hou
authors.affiliation: College of Pharmacy, Harbin Medical University, Daqing 163319, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Cao
authors.affiliation: College of Pharmacy, Harbin Medical University, Daqing 163319, China.
authors.forename: Shouli
authors.initials: S
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Harbin Medical University, Daqing 163319, China.
authors.forename: Fa
authors.initials: F
authors.lastname: He
authors.affiliation: College of Pharmacy, Harbin Medical University, Daqing 163319, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Song
authors.affiliation: College of Pharmacy, Harbin Medical University, Daqing 163319, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Pharmacy, Harbin Medical University, Daqing 163319, China. Electronic address: yuhuabai58@yahoo.com.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin, 150086 Heilongjiang, China. Electronic address: dalingz@yahoo.com.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D031187:Carthamus tinctorius; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D008517:Phytotherapy; D011651:Pulmonary Artery / Q000166:cytology / Q000473:pathology; D011809:Quinones / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D011809:Quinones; C085278:hydroxysafflor yellow A; D002599:Chalcone
keywords: HSYA; HSYA (PubChem CID: 6443665); Nifedipine (PubChem CID: 54167661); hypoxic pulmonary arterial hypertension; proliferation of PASMCs; pulmonary artery remodelling; right ventricular hypertrophy