Dataset Information

Proliferation and Recruitment Contribute to Myocardial Macrophage Expansion in Chronic Heart Failure.

ABSTRACT:

Rationale

Macrophages reside in the healthy myocardium, participate in ischemic heart disease, and modulate myocardial infarction (MI) healing. Their origin and roles in post-MI remodeling of nonischemic remote myocardium, however, remain unclear.

Objective

This study investigated the number, origin, phenotype, and function of remote cardiac macrophages residing in the nonischemic myocardium in mice with chronic heart failure after coronary ligation.

Methods and results

Eight weeks post MI, fate mapping and flow cytometry revealed that a 2.9-fold increase in remote macrophages results from both increased local macrophage proliferation and monocyte recruitment. Heart failure produced by extensive MI, through activation of the sympathetic nervous system, expanded medullary and extramedullary hematopoiesis. Circulating Ly6C(high) monocytes rose from 64±5 to 108±9 per microliter of blood (P<0.05). Cardiac monocyte recruitment declined in Ccr2(-/-) mice, reducing macrophage numbers in the failing myocardium. Mechanical strain of primary murine and human macrophage cultures promoted cell cycle entry, suggesting that the increased wall tension in post-MI heart failure stimulates local macrophage proliferation. Strained cells activated the mitogen-activated protein kinase pathway, whereas specific inhibitors of this pathway reduced macrophage proliferation in strained cell cultures and in the failing myocardium (P<0.05). Steady-state cardiac macrophages, monocyte-derived macrophages, and locally sourced macrophages isolated from failing myocardium expressed different genes in a pattern distinct from the M1/M2 macrophage polarization paradigm. In vivo silencing of endothelial cell adhesion molecules curbed post-MI monocyte recruitment to the remote myocardium and preserved ejection fraction (27.4±2.4 versus 19.1±2%; P<0.05).

Conclusions

Myocardial failure is influenced by an altered myeloid cell repertoire.

SUBMITTER: Sager HB

PROVIDER: S-EPMC5378496 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proliferation and Recruitment Contribute to Myocardial Macrophage Expansion in Chronic Heart Failure.

Sager Hendrik B HB Hulsmans Maarten M Lavine Kory J KJ Moreira Marina B MB Heidt Timo T Courties Gabriel G Sun Yuan Y Iwamoto Yoshiko Y Tricot Benoit B Khan Omar F OF Dahlman James E JE Borodovsky Anna A Fitzgerald Kevin K Anderson Daniel G DG Weissleder Ralph R Libby Peter P Swirski Filip K FK Nahrendorf Matthias M

Circulation research 20160721 7

<h4>Rationale</h4>Macrophages reside in the healthy myocardium, participate in ischemic heart disease, and modulate myocardial infarction (MI) healing. Their origin and roles in post-MI remodeling of nonischemic remote myocardium, however, remain unclear.<h4>Objective</h4>This study investigated the number, origin, phenotype, and function of remote cardiac macrophages residing in the nonischemic myocardium in mice with chronic heart failure after coronary ligation.<h4>Methods and results</h4>Eig ...[more]

PMID: 27444755

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Dataset Information

Proliferation and Recruitment Contribute to Myocardial Macrophage Expansion in Chronic Heart Failure.

Rationale

Objective

Methods and results

Conclusions

Publications

Proliferation and Recruitment Contribute to Myocardial Macrophage Expansion in Chronic Heart Failure.

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