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2014 ; 114
(2
): 266-82
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Remodeling of the mononuclear phagocyte network underlies chronic inflammation
and disease progression in heart failure: critical importance of the
cardiosplenic axis
#MMPMID24186967
Ismahil MA
; Hamid T
; Bansal SS
; Patel B
; Kingery JR
; Prabhu SD
Circ Res
2014[Jan]; 114
(2
): 266-82
PMID24186967
show ga
RATIONALE: The role of mononuclear phagocytes in chronic heart failure (HF) is
unknown. OBJECTIVE: Our aim was to delineate monocyte, macrophage, and dendritic
cell trafficking in HF and define the contribution of the spleen to cardiac
remodeling. METHODS AND RESULTS: We evaluated C57Bl/6 mice with chronic HF 8
weeks after coronary ligation. As compared with sham-operated controls, HF mice
exhibited: (1) increased proinflammatory CD11b+ F4/80+ CD206- macrophages and
CD11b+ F4/80+ Gr-1(hi) monocytes in the heart and peripheral blood, respectively,
and reduced CD11b+ F4/80+ Gr-1(hi) monocytes in the spleen; (2) significantly
increased CD11c+ B220- classical dendritic cells and CD11c+ low)B220+
plasmacytoid dendritic cells in both the heart and spleen, and increased classic
dendritic cells and plasmacytoid dendritic cells in peripheral blood and bone
marrow, respectively; (3) increased CD4+ helper and CD8+ cytotoxic T-cells in the
spleen; and (4) profound splenic remodeling with abundant white pulp follicles,
markedly increased size of the marginal zone and germinal centers, and increased
expression of alarmins. Splenectomy in mice with established HF reversed
pathological cardiac remodeling and inflammation. Splenocytes adoptively
transferred from mice with HF, but not from sham-operated mice, homed to the
heart and induced long-term left ventricular dilatation, dysfunction, and
fibrosis in naive recipients. Recipient mice also exhibited monocyte activation
and splenic remodeling similar to HF mice. CONCLUSIONS: Activation of mononuclear
phagocytes is central to the progression of cardiac remodeling in HF, and
heightened antigen processing in the spleen plays a critical role in this
process. Splenocytes (presumably splenic monocytes and dendritic cells) promote
immune-mediated injurious responses in the failing heart and retain this memory
on adoptive transfer.