title: Proinflammatory role of stem cells in abdominal aortic aneurysms.
abstract: OBJECTIVE
  The pathogenesis of abdominal aortic aneurysm (AAA) formation includes inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. That multipotent stem cells have an important role in cardiovascular health and disease has been well established, but the role of stem cells in aortic structural deterioration is poorly defined. We sought to describe the presence of stem cells in human AAA tissue and also investigated the differentiation of stem cells within the aneurysmal aorta.
  
  
  METHODS
  Infrarenal aortic wall specimens were collected from patients (n = 7) undergoing open AAA surgical repair. Nonaneurysmal infrarenal aortic control samples (n = 4) were collected at autopsies. Using immunohistochemistry, we compared the abundance of Stro1-positive ((+)), c-kit(+), and CD34(+) cells in aortic tissue. Using double-immunofluorescence staining, we evaluated stem cell differentiation into smooth muscle cells (SM22), fibroblasts (FSP1), and macrophages (CD68). We then investigated the colocalization of CD68(+) cells with the cellular marker of proliferation Ki67.
  
  
  RESULTS
  The media and adventitia of infrarenal AAA samples both demonstrated a significantly greater number of c-kit(+) and CD34(+) cells compared with matched control nonaneurysmal aortic tissues; however, the abundance of Stro1(+) cells was not significantly different between the groups. Using double-immunofluorescence staining, we identified that AAA stem cells express the macrophage marker CD68 but not the smooth muscle cell marker SM22 or the fibroblast marker FSP1. CD68(+) cells within the aortic wall colocalized with the cellular marker of proliferation Ki67.
  
  
  CONCLUSIONS
  Stem cells are significantly elevated in infrarenal AAA tissue compared with matched control aortic tissue. Our data also demonstrate that AAA stem cells express macrophage surface antigens but not smooth muscle cell or fibroblast markers. Furthermore, CD68(+) cells within the aortic wall colocalized with the cellular marker of proliferation Ki67. These finding suggest an inflammatory/immune role of stem cells during AAA pathogenesis and raise the possibility of localized replenishment therapy within the aneurysm wall.
authors.affiliation: Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, Pa. Electronic address: ejryer@geisinger.edu.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Ryer
authors.affiliation: Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, Pa.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Garvin
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pa.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Schworer
authors.affiliation: Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, Pa.
authors.forename: Kamell R
authors.initials: KR
authors.lastname: Bernard-Eckroth
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pa.
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.affiliation: Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, Pa.
authors.forename: David P
authors.initials: DP
authors.lastname: Franklin
authors.affiliation: Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, Pa.
authors.forename: James R
authors.initials: JR
authors.lastname: Elmore
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pa.
authors.forename: Helena
authors.initials: H
authors.lastname: Kuivaniemi
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000032:analysis; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D019394:Ki-67 Antigen / Q000032:analysis; D008264:Macrophages / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis; D008875:Middle Aged; D009124:Muscle Proteins / Q000032:analysis; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000473:pathology; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D000071999:S100 Calcium-Binding Protein A4; D013234:Stem Cells / Q000737:chemistry / Q000473:pathology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D000954:Antigens, Surface; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D009124:Muscle Proteins; D019009:Proto-Oncogene Proteins c-kit; D000071999:S100 Calcium-Binding Protein A4; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C525591:STRO-1 antigen, human; C051615:transgelin; C077591:S100A4 protein, human