title: A novel mouse model of aortic valve stenosis induced by direct wire injury.
abstract: OBJECTIVE
  The response-to-tissue-injury theory is currently the favorite paradigm to investigate valve pathology. To the best of our knowledge, there are currently no in vivo valve injury models. There are few calcific aortic valve stenosis (AVS) models that develop hemodynamically significant stenosis. Here, we investigated the effect of direct mechanical injury on aortic valves in vivo and developed a novel mouse model of calcific AVS.
  
  
  RESULTS
  Aortic valve injury was created by inserting and moving a spring guidewire under echocardiographic guidance into the left ventricle of male C57/BL6 mice via right common carotid artery. Serial echocardiographic measurements revealed that aortic velocity was increased 1 week after injury and persistently increased until 16 weeks after injury. AVS mice showed a higher heart weight/body weight ratio and decreased left ventricular fractioning shortening 4 weeks after injury, compared with sham mice. We found remarkable proliferation of valve leaflets 4 weeks after injury. Proliferative valves showed increased production of reactive oxygen species and expression of inflammatory cytokines and osteochondrogenic factors. Alizarin red staining showed valvular calcification 12 weeks after injury.
  
  
  CONCLUSIONS
  We report a novel calcific AVS model to support the response-to-tissue-injury theory. This model may be a valuable tool for analyzing the mechanism of AVS and assessing therapeutic options.
authors: From the Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors: Shintaro
authors: S
authors: Honda
authors: Takuya
authors: T
authors: Miyamoto
authors: Tetsu
authors: T
authors: Watanabe
authors: Taro
authors: T
authors: Narumi
authors: Shinpei
authors: S
authors: Kadowaki
authors: Yuki
authors: Y
authors: Honda
authors: Yoichiro
authors: Y
authors: Otaki
authors: Hiromasa
authors: H
authors: Hasegawa
authors: Shunsuke
authors: S
authors: Netsu
authors: Akira
authors: A
authors: Funayama
authors: Mitsunori
authors: M
authors: Ishino
authors: Satoshi
authors: S
authors: Nishiyama
authors: Hiroki
authors: H
authors: Takahashi
authors: Takanori
authors: T
authors: Arimoto
authors: Tetsuro
authors: T
authors: Shishido
authors: Takehiko
authors: T
authors: Miyashita
authors: Isao
authors: I
authors: Kubota
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000293:injuries* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation; D020219:Chondrogenesis; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D006335:Heart Injuries / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012720:Severity of Illness Index; D013318:Stroke Volume; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species
keywords: animal model; aortic valve stenosis; calcification