Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling

Atsushi Anzai, Toshihisa Anzai, Shigenori Nagai, Yuichiro Maekawa, Kotaro Naito, Hidehiro Kaneko, Yasuo Sugano, Toshiyuki Takahashi, Hitoshi Abe, Satsuki Mochizuki, Motoaki Sano, Tsutomu Yoshikawa, Yasunori Okada, Shigeo Koyasu, Satoshi Ogawa, Keiichi Fukuda

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Abstract

Background: Inflammation and immune responses are integral components in the healing process after myocardial infarction. We previously reported dendritic cell (DC) infiltration in the infarcted heart; however, the precise contribution of DC in postinfarction healing is unclear. Methods and Results: Bone marrow cells from CD11c-diphtheria toxin receptor/green fluorescent protein transgenic mice were transplanted into lethally irradiated wild-type recipient mice. After reconstitution of bone marrow-derived cells, the recipient mice were treated with either diphtheria toxin (DC ablation) or vehicle (control), and myocardial infarction was created by left coronary ligation. CD11c + green fluorescent protein-positive DCs expressing CD11b and major histocompatibility complex class II were recruited into the heart, peaking on day 7 after myocardial infarction in the control group. Mice with DC ablation for 7 days showed deteriorated left ventricular function and remodeling. The DC-ablated group demonstrated enhanced and sustained expression of inflammatory cytokines such as interleukin-1β, interleukin-18, and tumor necrosis factor-α, prolonged extracellular matrix degradation associated with a high level of matrix metalloproteinase-9 activity, and diminished expression level of interleukin-10 and endothelial cell proliferation after myocardial infarction compared with the control group. In vivo analyses revealed that DC-ablated infarcts had enhanced monocyte/macrophage recruitment. Among these cells, marked infiltration of proinflammatory Ly6C high monocytes and F4/80 + CD206 - M1 macrophages and, conversely, impaired recruitment of anti-inflammatory Ly6C low monocytes and F4/80 + CD206 + M2 macrophages in the infarcted myocardium were identified in the DC-ablated group compared with the control group. Conclusions - These results suggest that the DC is a potent immunoprotective regulator during the postinfarction healing process via its control of monocyte/macrophage homeostasis.

Original languageEnglish
Pages (from-to)1234-1245
Number of pages12
JournalCirculation
Volume125
Issue number10
DOIs
Publication statusPublished - 2012 Mar 13

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Keywords

  • Heart failure
  • Immune system
  • Inflammation
  • Myocardial infarction
  • Remodeling

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Anzai, A., Anzai, T., Nagai, S., Maekawa, Y., Naito, K., Kaneko, H., Sugano, Y., Takahashi, T., Abe, H., Mochizuki, S., Sano, M., Yoshikawa, T., Okada, Y., Koyasu, S., Ogawa, S., & Fukuda, K. (2012). Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling. Circulation, 125(10), 1234-1245. https://doi.org/10.1161/CIRCULATIONAHA.111.052126