• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pulmonary Circulation >Imatinib in Pulmonary Arterial Hypertension: C-Kit Inhibition:
【24h】

Imatinib in Pulmonary Arterial Hypertension: C-Kit Inhibition:

机译：伊马替尼在肺动脉高压中的作用：C-Kit抑制作用：

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by severe remodeling of the pulmonary artery resulting in increased pulmonary artery pressure and right ventricular hypertrophy and, ultimately, failure. Bone marrow–derived progenitor cells play a critical role in vascular homeostasis and have been shown to be involved in the pathogenesis of PAH. A proliferation of c-Kit+ hematopoietic progenitors and mast cells has been noted in the remodeled vessels in PAH. Imatinib, a tyrosine kinase inhibitor that targets c-Kit, has been shown to be beneficial for patients with PAH. Here we hypothesize that the clinical benefit of imatinib in PAH could be related to c-Kit inhibition of progenitor cell mobilization and maturation into mast cells. As a corollary to the phase 3 study using imatinib in PAH, blood samples were collected from 12 patients prior to starting study drug (baseline) and while on treatment at weeks 4 and 24. Eight were randomized to imatinib and 4 to placebo. Circulating c-Kit+ and CD34+ CD133+ hematopoietic progenitors as well as biomarkers of mast cell numbers and activation were measured. Circulating CD34+ CD133+ and c-Kit+ progenitor cells as well as c-Kit+/CD34+ CD133+ decreased with imatinib therapy (all P 0.05). In addition, total tryptase, a marker of mast cell load, dropped with imatinib therapy (P = 0.02) and was related to pulmonary vascular resistance (R = 0.7, P = 0.02). The findings support c-Kit inhibition as a potential mechanism of action of imatinib in PAH and suggest that tryptase is a potential biomarker of response to therapy.
机译：肺动脉高压（PAH）是一种进行性疾病，其特征是肺动脉严重重塑，导致肺动脉压升高和右心室肥大，并最终导致衰竭。骨髓来源的祖细胞在血管稳态中起着关键作用，并已证明与PAH的发病机制有关。在PAH的重塑血管中已注意到c-Kit +造血祖细胞和肥大细胞的增殖。伊马替尼是一种靶向c-Kit的酪氨酸激酶抑制剂，已被证明对PAH患者有益。在这里，我们假设伊马替尼在PAH中的临床获益可能与c-Kit抑制祖细胞动员和成熟进入肥大细胞有关。作为在PAH中使用伊马替尼的3期研究的必然结果，在开始研究药物之前（基线）以及在治疗的第4周和第24周时，从12位患者中收集了血液样本。将8位患者随机分配给伊马替尼，将4位随机给予安慰剂。测量循环中的c-Kit +和CD34 + CD133 +造血祖细胞以及肥大细胞数量和激活的生物标志物。伊马替尼治疗可使循环中的CD34 + CD133 +和c-Kit +祖细胞以及c-Kit + / CD34 + CD133 +减少（所有P <0.05）。此外，伊马替尼治疗后总的类胰蛋白酶（肥大细胞负荷的标志物）下降（P = 0.02），并且与肺血管阻力有关（R = 0.7，P = 0.02）。这些发现支持c-Kit抑制是伊马替尼在PAH中的潜在作用机制，并表明类胰蛋白酶是对治疗反应的潜在生物标记。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号