IFN-gamma primes intact human coronary arteries and cultured coronary smooth muscle cells to double-stranded RNA- and self-RNA-induced inflammatory responses by upregulating TLR3 and melanoma differentiation-associated gene 5.

Atherosclerosis of native coronary arteries and graft arteriosclerosis in transplanted hearts are characterized by activation of innate and adaptive immune responses. Nucleic acids generated by infections or cell death have been detected within arteriosclerotic lesions, and it is known that microbial and synthetic nucleic acids evoke inflammatory responses in cultured vascular cells. In this study, we report that model RNA, but not DNA, instigated robust cytokine and chemokine production from intact human coronary arteries containing both intrinsic vascular cells and resident/infiltrating leukocytes.

Heparin displaces interferon-gamma-inducible chemokines (IP-10, I-TAC, and Mig) sequestered in the vasculature and inhibits the transendothelial migration and arterial recruitment of T cells.

Background: Heparin, used clinically as an anticoagulant, also has antiinflammatory properties and has been described to inhibit interferon (IFN)-gamma responses in endothelial cells. We investigated the effects of heparin on the IFN-gamma-inducible chemokines IP-10/CXCL10, I-TAC/CXCL11, and Mig/CXCL9, which play important roles in the vascular recruitment of IFN-gamma-producing Th1 cells through interactions with their cognate receptor, CXCR3.

Methods And Results: Patients undergoing coronary artery bypass grafting were studied because coronary atherosclerosis is recognized as a Th1-type inflammatory disease and the subjects required systemic heparinization.

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.