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-γ 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.