Abstract：
UNASSIGNED: Patients with JAK2V617F-positive myeloproliferative neoplasms (MPNs) and clonal hematopoiesis of indeterminate potential face a significantly elevated risk of cardiovascular diseases. Endothelial cells carrying the JAK2V617F mutation have been detected in many patients with MPN. In this study, we investigated the molecular basis for the high incidence of cardiovascular complications in patients with MPN.
UNASSIGNED: We investigated the impact of endothelial JAK2V617F mutation on cardiovascular disease development using both transgenic murine models and MPN patient-derived induced pluripotent stem cell lines.
UNASSIGNED: Our investigations revealed that JAK2V617F mutant endothelial cells promote cardiovascular diseases under stress, which is associated with endothelial-to-mesenchymal transition and endothelial dysfunction. Importantly, we discovered that inhibiting the endothelial TPO (thrombopoietin) receptor MPL suppressed JAK2V617F-induced endothelial-to-mesenchymal transition and prevented cardiovascular dysfunction caused by mutant endothelial cells. Notably, the endothelial MPL receptor is not essential for the normal physiological regulation of blood cell counts and cardiac function.
UNASSIGNED: JAK2V617F mutant endothelial cells play a critical role in the development of cardiovascular diseases in JAK2V617F-positive MPNs, and endothelial MPL could be a promising therapeutic target for preventing or ameliorating cardiovascular complications in these patients.
UNASSIGNED: We investigated the impact of endothelial JAK2V617F mutation on cardiovascular disease development using both transgenic murine models and MPN patient-derived induced pluripotent stem cell lines.
UNASSIGNED: Our investigations revealed that JAK2V617F mutant endothelial cells promote cardiovascular diseases under stress, which is associated with endothelial-to-mesenchymal transition and endothelial dysfunction. Importantly, we discovered that inhibiting the endothelial TPO (thrombopoietin) receptor MPL suppressed JAK2V617F-induced endothelial-to-mesenchymal transition and prevented cardiovascular dysfunction caused by mutant endothelial cells. Notably, the endothelial MPL receptor is not essential for the normal physiological regulation of blood cell counts and cardiac function.
UNASSIGNED: JAK2V617F mutant endothelial cells play a critical role in the development of cardiovascular diseases in JAK2V617F-positive MPNs, and endothelial MPL could be a promising therapeutic target for preventing or ameliorating cardiovascular complications in these patients.
摘要：
■患有JAK2V617F阳性骨髓增殖性肿瘤（MPN）和克隆性造血功能不确定的患者患心血管疾病的风险显着升高。在许多MPN患者中检测到携带JAK2V617F突变的内皮细胞。在这项研究中,我们调查了MPN患者心血管并发症高发生率的分子基础.
我们使用转基因鼠模型和MPN患者来源的诱导多能干细胞系研究了内皮JAK2V617F突变对心血管疾病发展的影响。
■我们的研究表明，JAK2V617F突变内皮细胞在压力下促进心血管疾病，这与内皮-间质转化和内皮功能障碍有关。重要的是,我们发现,抑制内皮TPO(血小板生成素)受体MPL可抑制JAK2V617F诱导的内皮-间质转化,并预防由突变内皮细胞引起的心血管功能障碍.值得注意的是,内皮MPL受体对于血细胞计数和心脏功能的正常生理调节不是必需的。
■JAK2V617F突变内皮细胞在JAK2V617F阳性MPNs的心血管疾病发展中起关键作用，和内皮MPL可能是预防或改善这些患者心血管并发症的有希望的治疗靶点。
我们使用转基因鼠模型和MPN患者来源的诱导多能干细胞系研究了内皮JAK2V617F突变对心血管疾病发展的影响。
■我们的研究表明，JAK2V617F突变内皮细胞在压力下促进心血管疾病，这与内皮-间质转化和内皮功能障碍有关。重要的是,我们发现,抑制内皮TPO(血小板生成素)受体MPL可抑制JAK2V617F诱导的内皮-间质转化,并预防由突变内皮细胞引起的心血管功能障碍.值得注意的是,内皮MPL受体对于血细胞计数和心脏功能的正常生理调节不是必需的。
■JAK2V617F突变内皮细胞在JAK2V617F阳性MPNs的心血管疾病发展中起关键作用，和内皮MPL可能是预防或改善这些患者心血管并发症的有希望的治疗靶点。
