PMID: 30166715Sep 1, 2018Paper

THE CARDIOSPLENIC AXIS IS ESSENTIAL FOR THE PATHOGENESIS OF ISCHEMIC HEART FAILURE

Transactions of the American Clinical and Climatological Association
Sumanth D Prabhu

Abstract

The role of innate and adaptive immunity in heart failure (HF) is poorly understood. We discovered that mice with ischemic HF exhibit robust expansion of proinflammatory monocytes/macrophages, classical and plasmacytoid dendritic cells, and CD4+ and CD8+ T cells. There was profound splenic remodeling indicative of heightened antigen processing, and expanded antigen-experienced effector and memory CD4+ T cell populations. A series of subsequent studies in HF mice that incorporated splenectomy, adoptive transfer of both unselected splenocytes and splenic CD4+ T-cells, and antibody-mediated CD4+ T-cell depletion indicated that intensely activated splenic immune cells: 1) underlie the chronic inflammatory response in HF, 2) traffic and home to the failing heart, and 3) exhibit immune memory and are primed to induce tissue injury that promotes pathological cardiac remodeling. Hence, we propose that ischemic cardiomyopathy is in part an immune-mediated disease, against as-of-yet unidentified cardiac antigens, with a central role for the spleen in this process.

Related Concepts

Related Feeds

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Cardiac Remodeling

Cardiac remodeling in response to a myocardial infarction is characterized by progressive ventricular dilatation, cardiac hypertrophy, fibrosis, and deterioration of cardiac performance. Discover the latest research on Cardiac Remodeling here.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.