Left Ventricular T-Cell Recruitment Contributes to the Pathogenesis of Heart Failure. (July 2015)

• Record Type: Journal Article
• Authors: Nevers, Tania; Salvador, Ane M.; Grodecki-Pena, Anna; Knapp, Andrew; Velázquez, Francisco; Aronovitz, Mark; Kapur, Navin K.; Karas, Richard H.; Blanton, Robert M.; Alcaide, Pilar
• Is Part Of: Circulation. Volume 8:Number 4(2015)
• Publication Date: 2015-07
• Subjects: Heart failure -- Periodicals; 616.129005
• DOI: 10.1161/CIRCHEARTFAILURE.115.002225
• Languages: English
• ISSNs: 1941-3289

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background—</title> <p>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.</p> </sec> <sec> <title>Methods and Results—</title> <p>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, TCRα<sup>−/−</sup>) 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.</p> </sec> <sec> <title>Conclusions—</title> <p>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.</p> </sec> </abstract>