Cardiac hypertrophy associated with myeloproliferative neoplasms in JAK2V617F transgenic mice.
Cardiac hypertrophy associated with myeloproliferative neoplasms in JAK2V617F transgenic mice.
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JAK2V617F 转基因小鼠心脏肥大与骨髓增生性肿瘤相关
DOI：
10.1186/1756-8722-7-25
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发表时间：
2014-03-19
影响因子：
28.5
通讯作者：
Zhao ZJ
中科院分区：
文献类型：
--
作者：
Shi K;Zhao W;Chen Y;Ho WT;Yang P;Zhao ZJ
骨髓增生性肿瘤（Myeloproliferative neoplasia，MPN）是一种以红细胞、白色细胞和/或血小板生成增加为主要表现的血液恶性肿瘤。与疾病相关的主要分子损伤是JAK 2 V617 F，酪氨酸激酶JAK 2的活化突变形式。心血管事件的发病率和死亡率相关的MPN的主要原因，但其潜在的机制是不是很好地understood.MethodsPreviously，我们产生的JAK 2 V617 F转基因小鼠显示MPN样表型。在本研究中，我们通过分析MPN表型发展的时间进程和相关的心脏异常来进一步表征这些小鼠。结果JAK 2 V617 F转基因小鼠在MPN表型发育过程中，随着血细胞生成的增加，出现心脏肥大。心脏肥大表现为心室壁增厚和心肌细胞增大。三色和网硬蛋白染色显示JAK 2 V617 F转基因小鼠心脏中广泛的胶原纤维化。JAK 2 V617 F转基因小鼠中还观察到冠状动脉血栓形成和心肌炎性细胞浸润，后者伴有纤维化. ConclusionJAK 2 V617 F诱导的血液疾病对心脏功能有重大影响，并导致心脏肥大。JAK 2 V617 F转基因小鼠是研究血液恶性肿瘤和心血管疾病的良好模型系统。
BackgroundMyeloproliferative 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.MethodsPreviously, 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.ResultsJAK2V617F 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.ConclusionJAK2V617F-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.
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影响因子：
28.5
作者：
Talpaz M;Paquette R;Afrin L;Hamburg SI;Prchal JT;Jamieson K;Terebelo HR;Ortega GL;Lyons RM;Tiu RV;Winton EF;Natrajan K;Odenike O;Claxton D;Peng W;O'Neill P;Erickson-Viitanen S;Leopold L;Sandor V;Levy RS;Kantarjian HM;Verstovsek S
通讯作者：
Verstovsek S
影响因子：
3.7
作者：
Jin X;Zhao W;Shi K;Ho WT;Zhao ZJ
通讯作者：
Zhao ZJ
影响因子：
20.3
作者：
Beer PA;Erber WN;Campbell PJ;Green AR
通讯作者：
Green AR
影响因子：
20.3
作者：
Tefferi, Ayalew;Thiele, Juergen;Vardiman, James W.
通讯作者：
Vardiman, James W.
影响因子：
20.3
作者：
Ogilvy, S;Elefanty, AG;Adams, JM
通讯作者：
Adams, JM