Cardiac hypertrophy associated with myeloproliferative neoplasms in JAK2V617F transgenic mice

Journal of Hematology & Oncology

Zhizhuang Joe Zhao²  Ping Yang¹  Wanting Tina Ho²  Yun Chen²  Wanke Zhao²  Kaiyao Shi² 

[1] Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130021, China;Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA

关键词: Cardiac hypertrophy;    Cardiomegaly;    Fibrosis;    Hematological malignancies;    JAK2V617F;    MPN;   

Others  :  801619
DOI  :  10.1186/1756-8722-7-25

 received in 2014-02-10, accepted in 2014-03-15,  发布年份 2014

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2014 Shi et al.; licensee BioMed Central Ltd.

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