Local cytokine environments drive aneurysm formation in allografted aortas.
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.
Shimizu
Koichi
K
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
Libby
Peter
P
Mitchell
Richard N
RN
D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000637:transplantation*; D001014:Aortic Aneurysm / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D014184:Transplantation, Homologous
D016207:Cytokines