Serpin Treatment Suppresses Inflammatory Vascular Lesions in Temporal Artery Implants (TAI) from Patients with Giant Cell Arteritis PLOS ONE Chen, H., Zheng, D., Ambadapadi, S., Davids, J., Ryden, S., Samy, H., Bartee, M., Sobel, E., Dai, E., Liu, L., Macaulay, C., Yachnis, A., Weyand, C., Thoburn, R., Lucas, A. 2015; 10 (2)

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-1ß), IL-17, and CD25 and decreased Factor II. Serp-1 decreased IL-1ß 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-1ß.

View details for DOI 10.1371/journal.pone.0115482

View details for Web of Science ID 000349444900018

View details for PubMedID 25658487

View details for PubMedCentralID PMC4319900