Analysis of myxomaviral serpin treatment for inflammatory vasculitic syndromes, giant cell and takayasu arteritis

摘要

Inflammatory vasculitic syndromes (TVS), Giant cell arteritis and Takayasu's disease, cause sudden blindness and cerebral ischemia with limited available treatments. Two IVS models, gamma68 Herpes virus infected interferon gamma receptor deficient (IFNgammaR-KO) mice and human temporal arterial biopsy (TA) or left internal mammary artery (LIMA) implanted severe-conrbined-rmmunodeficient (SCID) mice were used to test response to treatment with serine poteinase inhibitors (serpins), myxomaviral Serp-1 and rnamrualian neuroserpin (NSP). Serp-1 inhibits uPA, tPA and factor Xa (fXa) while NSP only inhibits tPA and uPA. Ten days treatment with Serp-1, but not with NSP prolonged survival by 10 days in gamma68HV-infected mice with reductions in arterial and pulmonary inflammation and interleukin 1 beta. Serp-1 also reduced inflammatory cell invasion in LIMA xenografts. Serp-L effectively reduces inflammation or plaque growth in these TVS models with fXa representing a new therapeutic target for TVS.