title: Local cytokine environments drive aneurysm formation in allografted aortas.
abstract: The mechanistic differences between the pathways that induce stenotic vs. aneurysmal manifestations of atherosclerosis remain unknown. In a murine aortic interposition graft model, T helper cell type 1 (Th1)- vs. Th2-slanted cytokine environments differentially affected the vascular pathology; specifically, blockade of interferon-gamma signaling and/or Th2-enriched environments induced aneurysm formation associated with elastic tissue fragmentation. A Th2 cytokine milieu was shown to increase selected matrix metalloproteinase (MMP) expression, and interleukin 4 stimulated macrophage production of elastolytic matrix metalloproteinase 12 in vitro. The new findings establish important regulatory roles for a Th1/Th2 cytokine balance in modulating matrix remodeling, and have important implications for the pathophysiology of abdominal aortic aneurysms as well as atherosclerosis.
authors.affiliation: Cardiovascular Division, Department of Medicine, The Donald W. Reynolds Cardiovascular Clinical Research Center, Harvard Medical School, 77 Avenue Louis Pasteur, NRB7, Boston, MA 02115, USA. ksmz@rics.bwh.harvard.edu
authors.forename: Koichi
authors.initials: K
authors.lastname: Shimizu
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Richard N
authors.initials: RN
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000637:transplantation*; D001014:Aortic Aneurysm / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines