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Left Ventricular T-Cell Recruitment Contributes to the Pathogenesis of Heart Failure.

ABSTRACT: 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 nonischemic HF patients or from mice with HF induced by transverse aortic constriction 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 transverse aortic constriction and the kinetics of LV T-cell infiltration was directly associated with the development of systolic dysfunction. In response to transverse aortic constriction, T cell-deficient mice (T-cell receptor, TCR?(-/-)) had preserved LV systolic and diastolic function, reduced LV fibrosis, hypertrophy and inflammation, and improved survival compared with wild-type mice. Furthermore, T-cell depletion in wild-type mice after transverse aortic constriction prevented HF.T cells are major contributors to nonischemic 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.

SUBMITTER: Nevers T

PROVIDER: S-EPMC4512916 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Left Ventricular T-Cell Recruitment Contributes to the Pathogenesis of Heart Failure.

Nevers Tania T Salvador Ane M AM Grodecki-Pena Anna A Knapp Andrew A Velázquez Francisco F Aronovitz Mark M Kapur Navin K NK Karas Richard H RH Blanton Robert M RM Alcaide Pilar P

Circulation. Heart failure 20150528 4

<h4>Background</h4>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.<h4>Methods and results</h4>Real-time videomicroscopy of T cells from nonischemi ...[more]

PMID: 26022677

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Dataset Information

Left Ventricular T-Cell Recruitment Contributes to the Pathogenesis of Heart Failure.

Publications

Left Ventricular T-Cell Recruitment Contributes to the Pathogenesis of Heart Failure.

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