Deciphering the stromal and hematopoietic cell network of the adventitia from non-aneurysmal and aneurysmal human aorta

PLoS One. 2014 Feb 27;9(2):e89983. doi: 10.1371/journal.pone.0089983. eCollection 2014.

Abstract

Aneurysm is associated to a complex remodeling of arteries that affects all their layers. Although events taking place in the intima and the media have received a particular attention, molecular and cellular events taking place in the adventitia have started to be deciphered only recently. In this study, we have precisely described the composition and distribution of stromal and hematopoietic cells in human arterial adventitia, both at steady state and in the setting of aortic aneurysm. Using polychromatic immunofluorescent and flow cytometry analyses, we observed that unlike the medial layer (which comprises mostly macrophages and T cells among leukocytes), the adventitia comprises a much greater variety of leukocytes. We observed an altered balance in macrophages subsets in favor of M2-like macrophages, an increased proliferation of macrophages, a greater number of all stromal cells in aneurysmal aortas. We also confirmed that in this pathological setting, adventitia comprised blood vessels and arterial tertiary lymphoid organs (ATLOs), which contained also M-DC8(+) dendritic cells (slanDCs) that could participate in the induction of T-cell responses. Finally, we showed that lymphatic vessels can be detected in aneurysmal adventitia, the functionality of which will have to be evaluated in future studies. All together, these observations provide an integrative outlook of the stromal and hematopoietic cell network of the human adventitia both at steady state and in the context of aneurysm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adventitia / cytology*
  • Adventitia / metabolism
  • Aortic Aneurysm / metabolism
  • Aortic Aneurysm / pathology*
  • Humans
  • Immunophenotyping
  • Leukocytes* / metabolism
  • Stromal Cells* / metabolism

Grants and funding

This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), the Paris Denis Diderot University, the Région Ile de France (CORDDIM), the Fondation de la Recherche Médicale (FRM), and the Agence Nationale de la Recherche (ANR, grant ‘MI2 ‘ATHLO’). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.