Inflammation and cellular immune responses in abdominal aortic aneurysms.
Expansion and rupture of abdominal aortic aneurysms (AAA) result in high morbidity and mortality rates. Like stenotic atherosclerotic lesions, AAA accumulate inflammatory cells, but usually exhibit much more extensive medial damage. Leukocyte recruitment and expression of pro-inflammatory Th1 cytokines typically characterize early atherogenesis of any kind, and modulation of inflammatory mediators mutes atheroma formation in mice. However, the mechanistic differences between stenotic and aneurysmal manifestations of atherosclerosis remain unexplained. We recently showed that aortic allografts deficient in interferon-gamma (IFN-gamma) signaling developed AAA correlating with skewed Th2 cytokine environments, suggesting important regulatory roles for Th1/Th2 cytokine balance in modulating matrix remodeling and important implications for the pathophysiology of aortic aneurysm and atherosclerosis. Further probing of their distinct aspects of immune and inflammatory responses in vascular diseases should continue to shed new light on the pathophysiologic mechanisms that give rise to aneurysmal versus occlusive manifestations and atherosclerosis.
Shimizu
Koichi
K
The Donald W. Reynolds Cardiovascular Clinical Research Center, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ksmz@rics.bwh.harvard.edu
Mitchell
Richard N
RN
Libby
Peter
P
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology* / Q000276:immunology* / Q000517:prevention & control; D050197:Atherosclerosis / Q000150:complications; D002403:Cathepsins / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000150:complications*; D007371:Interferon-gamma / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000502:physiology; D010196:Pancreatic Elastase / Q000502:physiology; D015398:Signal Transduction
D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma; D003094:Collagen; D002403:Cathepsins; D010196:Pancreatic Elastase; D020782:Matrix Metalloproteinases