Left Ventricular T-Cell Recruitment Contributes to the Pathogenesis of Heart Failure.
Left Ventricular T-Cell Recruitment Contributes to the Pathogenesis of Heart Failure.
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DOI：
10.1161/circheartfailure.115.002225
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Alcaide P
中科院分区：
文献类型：
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作者：
Nevers T;Salvador AM;Grodecki-Pena A;Knapp A;Velázquez F;Aronovitz M;Kapur NK;Karas RH;Blanton RM;Alcaide P
尽管心力衰竭（HF）和炎症之间的联系正在出现，但T细胞（慢性炎症的主要参与者）的作用直到最近才开始探索。T细胞募集到左心室（LV）是否参与HF的发展需要进一步研究，以确定新的机制，可能有助于替代治疗干预的设计。来自非缺血性HF患者或来自患有由横向主动脉缩窄（TAC）诱导的HF的小鼠的T细胞的真实的时间视频显微镜显示，与来自健康受试者或假手术小鼠的T细胞相比，在体外流动条件下与活化的血管内皮细胞的粘附增强。T细胞在纵隔淋巴结和心肌内的内皮细胞都被激活响应TAC和LV T细胞浸润的动力学与收缩功能障碍的发展直接相关。作为对TAC的反应，与WT小鼠相比，T细胞缺陷小鼠（TCRα−/−）保留了LV收缩和舒张功能，减少了LV纤维化、肥大和炎症，并提高了存活率。此外，TAC后WT小鼠中的T细胞耗竭预防了HF。T细胞是非缺血性HF的主要贡献者。它们的活化与LV内皮的活化相结合，导致LV T细胞浸润，通过涉及细胞因子释放和诱导心脏纤维化和肥大的机制，对HF进展产生负面影响。因此，T细胞浸润的减少被鉴定为HF中的新的翻译靶点。
Despite the emerging association between Heart Failure (HF) and inflammation, the role of T cells, major players in chronic inflammation, has only recently begun to be explored. Whether T cell recruitment to the left ventricle (LV) participates in the development of HF requires further investigation to identify novel mechanisms that may serve for the design of alternative therapeutic interventions. Real time videomicroscopy of T cells from non- ischemic HF patients or from mice with HF induced by transverse aortic constriction (TAC) revealed enhanced adhesion to activated vascular endothelial cells under flow conditions in vitro compared with T cells from healthy subjects or sham mice. T cells in the mediastinal lymph nodes and the intramyocardial endothelium were both activated in response to TAC and the kinetics of LV T cell infiltration was directly associated with the development of systolic dysfunction. In response to TAC, T cell deficient mice (TCRα−/−) had preserved LV systolic and diastolic function, reduced LV fibrosis, hypertrophy and inflammation, and improved survival compared to WT mice. Furthermore T cell depletion in WT mice after TAC prevented HF. T cells are major contributors to non-ischemic HF. Their activation combined with the activation of the LV endothelium results in LV T cell infiltration negatively contributing to HF progression through mechanisms involving cytokine release and induction of cardiac fibrosis and hypertrophy. Reduction of T cell infiltration is thus identified as a novel translational target in HF.