In:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 282, No. 1 ( 2002-01-01), p. R166-R172
Abstract:
Patients with heart failure are predisposed to infections and anemia, possibly due to reduced hematopoiesis. The proinflammatory cytokine tumor necrosis factor-α (TNF-α) is increased in heart failure, and it inhibits normal hematopoiesis, partly due to apoptosis through the effector molecule Fas. We examined bone marrow progenitor cells of mice with heart failure induced by acute myocardial infarction. The fraction of progenitor cells in mice with heart failure was only ∼40% of control. Measured with in vitro clonal assays, the proliferative capacity of the progenitor cells in mice with heart failure was reduced to ∼50% of control. Flow cytometry with specific markers revealed a threefold increase in apoptosis among progenitor cells from mice with heart failure. In these mice, TNF-α/Fas expression was increased in bone marrow natural killer (NK) and T cells, and these lymphocytes showed increased cytolytic activity in vitro against progenitor cells. We conclude that the TNF-α/Fas pathway in lymphocytes is activated in the bone marrow during heart failure, which may play a pathogenic role in the observed decrease in hematopoiesis.
Type of Medium:
Online Resource
ISSN:
0363-6119
,
1522-1490
DOI:
10.1152/ajpregu.2002.282.1.R166
Language:
English
Publisher:
American Physiological Society
Publication Date:
2002
detail.hit.zdb_id:
1477297-8
SSG:
12
