Decreased myocardial dendritic cells is associated with impaired reparative fibrosis and development of cardiac rupture after myocardial infarction in humans

J Am Heart Assoc. 2014 Jun 3;3(3):e000839. doi: 10.1161/JAHA.114.000839.

Abstract

Background: Dendritic cells (DC) play pivotal roles in regulating the immune system and inflammatory response. We previously reported DC infiltration in the infarcted heart and its immunoprotective roles in the post-infarction healing process after experimental myocardial infarction (MI). However, its clinical significance has not been determined.

Methods and results: The degree of DC infiltration and its correlation with the post-infarction healing process in the human infarcted heart were investigated in 24 autopsy subjects after ST-elevation MI. Patients were divided into two groups according to the presence (n=13) or absence (n=11) of cardiac rupture. The numbers of infiltrated DC and macrophages and the extent of fibrosis in the infarcted area were examined. In the rupture group, CD68(+) macrophage infiltration was increased and CD209(+) DC, and CD11c(+) DC infiltration and the extent of reparative fibrosis were decreased compared with the non-rupture group, under matched baseline characteristics including the time from onset to death and use of revascularization. Furthermore, there was a significant positive correlation between the number of infiltrating CD209(+) DC, and CD11c(+) DC and the extent of reparative fibrosis.

Conclusions: Decreased number of DC in human-infarcted myocardial tissue was associated with increased macrophage infiltration, impaired reparative fibrosis, and the development of cardiac rupture after MI. These findings suggest a protective role of DC in post-MI inflammation and the subsequent healing process.

Keywords: cardiac rupture; dendritic cell; inflammation; myocardial infarction; reparative fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / physiology
  • Antigens, Differentiation, Myelomonocytic / physiology
  • Case-Control Studies
  • Cell Adhesion Molecules / physiology
  • Dendritic Cells / pathology*
  • Dendritic Cells / physiology
  • Female
  • Fibrosis
  • Heart / physiopathology
  • Heart Rupture, Post-Infarction / etiology*
  • Heart Rupture, Post-Infarction / pathology
  • Heart Rupture, Post-Infarction / physiopathology
  • Humans
  • Lectins, C-Type / physiology
  • Macrophages / pathology
  • Macrophages / physiology
  • Male
  • Myocardial Infarction / complications*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardium / cytology
  • Myocardium / pathology*
  • Receptors, Cell Surface / physiology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Cell Surface