title: Serpin treatment suppresses inflammatory vascular lesions in temporal artery implants (TAI) from patients with giant cell arteritis.
abstract: Giant cell arteritis (GCA) and Takayasu's disease are inflammatory vasculitic syndromes (IVS) causing sudden blindness and widespread arterial obstruction and aneurysm formation. Glucocorticoids and aspirin are mainstays of treatment, predominantly targeting T cells. Serp-1, a Myxomavirus-derived serpin, blocks macrophage and T cells in a wide range of animal models. Serp-1 also reduced markers of myocardial injury in a Phase IIa clinical trial for unstable coronary disease. In recent work, we detected improved survival and decreased arterial inflammation in a mouse Herpesvirus model of IVS. Here we examine Serp-1 treatment of human temporal artery (TA) biopsies from patients with suspected TA GCA arteritis after implant (TAI) into the aorta of immunodeficient SCID (severe combined immunodeficiency) mice. TAI positive for arteritis (GCApos) had significantly increased inflammation and plaque when compared to negative TAI (GCAneg). Serp-1 significantly reduced intimal inflammation and CD11b+ cell infiltrates in TAI, with reduced splenocyte Th1, Th17, and Treg. Splenocytes from mice with GCApos grafts had increased gene expression for interleukin-1 beta (IL-1β), IL-17, and CD25 and decreased Factor II. Serp-1 decreased IL-1β expression. In conclusion, GCApos TAI xenografts in mice provide a viable disease model and have increased intimal inflammation as expected and Serp-1 significantly reduces vascular inflammatory lesions with reduced IL-1β.
authors: Department of Medicine, University of Florida, Gainesville, Florida, United States of America; Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida, United States of America.
authors: Hao
authors: H
authors: Chen
authors: Department of Medicine, University of Florida, Gainesville, Florida, United States of America; Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida, United States of America.
authors: Donghang
authors: D
authors: Zheng
authors: Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors: Sriram
authors: S
authors: Ambadapadi
authors: Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors: Jennifer
authors: J
authors: Davids
authors: Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors: Sally
authors: S
authors: Ryden
authors: Department of Ophthalmology, University of Florida, Gainesville, Florida, United States of America.
authors: Hazem
authors: H
authors: Samy
authors: Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors: Mee
authors: M
authors: Bartee
authors: Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors: Eric
authors: E
authors: Sobel
authors: Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors: Erbin
authors: E
authors: Dai
authors: Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors: Liying
authors: L
authors: Liu
authors: Viron Therapeutics, London, Ontario, Canada.
authors: Colin
authors: C
authors: Macaulay
authors: Department of Pathology, University of Florida, Gainesville, Florida, United States of America.
authors: Anthony
authors: A
authors: Yachnis
authors: Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, United States of America.
authors: Cornelia
authors: C
authors: Weyand
authors: Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors: Robert
authors: R
authors: Thoburn
authors: Department of Medicine, University of Florida, Gainesville, Florida, United States of America; Department of Ophthalmology, University of Florida, Gainesville, Florida, United States of America; Viron Therapeutics, London, Ontario, Canada.
authors: Alexandra
authors: A
authors: Lucas
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D013700:Giant Cell Arteritis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015843:Serpins / Q000494:pharmacology*; D013625:Takayasu Arteritis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013699:Temporal Arteries / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D014764:Viral Proteins / Q000494:pharmacology*
chemical_list: D015843:Serpins; D014764:Viral Proteins