title: Cardiac hypertrophy associated with myeloproliferative neoplasms in JAK2V617F transgenic mice.
abstract: BACKGROUND
  Myeloproliferative neoplasms (MPNs) are blood malignancies manifested in increased production of red blood cells, white blood cells, and/or platelets. A major molecular lesion associated with the diseases is JAK2V617F, an activation mutation form of tyrosine kinase JAK2. Cardiovascular events represent the leading cause of morbidity and mortality associated MPNs, but the underlying mechanism is not well understood.
  
  
  METHODS
  Previously, we generated JAK2V617F transgenic mice which displayed MPN-like phenotypes. In the present study, we further characterized these mice by analyzing the time course of MPN phenotype development and associated cardiac abnormalities. We performed detailed histochemical staining of cardiac sections.
  
  
  RESULTS
  JAK2V617F transgenic mice developed cardiomegaly as a subsequent event of increased blood cell production during the course of MPN phenotype development. The cardiomegaly is manifested in increased ventricular wall thickness and enlarged cardiomyocytes. Trichrome and reticulin staining revealed extensive collagen fibrosis in the heart of JAK2V617F transgenic mice. Thrombosis in the coronary artery and inflammatory cell infiltration into cardiac muscle were also observed in JAK2V617F transgenic mice, and the latter event was accompanied by fibrosis.
  
  
  CONCLUSIONS
  JAK2V617F-induced blood disorders have a major impact on heart function and lead to cardiac hypertrophy. JAK2V617F transgenic mice represent an excellent model system to study both hematological malignancies and cardiovascular diseases.
authors.forename: Kaiyao
authors.initials: K
authors.lastname: Shi
authors.forename: Wanke
authors.initials: W
authors.lastname: Zhao
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Wanting Tina
authors.initials: WT
authors.lastname: Ho
authors.affiliation: Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130021, China. pyang@jlu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Zhizhuang Joe
authors.initials: ZJ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D019337:Hematologic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D053614:Janus Kinase 2