Transmural inflammation by interferon-gamma-producing T cells correlates with outward vascular remodeling and intimal expansion of ascending thoracic aortic aneurysms.
Arterial pathology manifests as aneurysmal or obstructive disease depending on changes in lumen size due to vascular remodeling (change in vessel external diameter) and/or intimal expansion. Recent clinical and experimental observations in abdominal aortic aneurysms have led to the emerging dogma that Th2-dominant immune responses result in expansive vascular remodeling and luminal ectasia, whereas Th1 immune responses cause intimal hyperplasia and luminal stenosis. We tested this hypothesis by descriptive analyses of 31 non-aneurysmal and 29 aneurysmal ascending thoracic aortic specimens. Approximately half the aneurysms were distinguished by transmural inflammation. The remaining aneurysms and all the non-aneurysmal aortas had a similar leukocytic infiltrate that spared the inner media. Aneurysm tissue had increased expression of the prototypical Th1 cytokine, interferon (IFN)-gamma, and undetectable Th2 cytokines. Specimens with inner media infiltration displayed robust production of IFN-gamma, induction of the IFN-gamma-inducible chemokines IP-10 and Mig, and recruitment of lymphocytes bearing their cognate receptor CXCR3. Transmural inflammation and IFN-gamma production were associated with increased aortic external diameter, intimal thickening, preserved vascular smooth muscle cell density, and decreased matrix proteins. Th1, but not Th2, immune responses have a positive correlation with both outward vascular remodeling and intimal expansion of ascending thoracic aortic aneurysms.
Tang
Paul C Y
PC
Interdepartmental Program in Vascular Biology and Transplantation, Yale University School of Medicine, New Haven, Connecticut, USA.
Yakimov
Alexander O
AO
Teesdale
Michael A
MA
Coady
Michael A
MA
Dardik
Alan
A
Elefteriades
John A
JA
Tellides
George
G
D000293:Adolescent; D000328:Adult; D017545:Aortic Aneurysm, Thoracic / Q000276:immunology / Q000473:pathology*; D001483:Base Sequence; D019002:CD56 Antigen / Q000032:analysis; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000473:pathology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007962:Leukocytes / Q000473:pathology; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D017539:Tunica Intima / Q000473:pathology*
D019002:CD56 Antigen; D016326:Extracellular Matrix Proteins; D007371:Interferon-gamma