title: Endothelial cells, fibroblasts and vasculitis.
abstract: One of the most important questions in vasculitis research is not why inflammation of blood vessels occurs but why it persists, often in a site-specific manner. In this review we illustrate how stromal cells, such as fibroblasts and pericytes, might play an important role in regulating the site at which vasculitis occurs. Smooth muscle cells and fibroblasts directly influence the behaviour of overlying vascular cells, amplifying the response of the endothelium to proinflammatory agents such as TNF-alpha and allowing enhanced and inappropriate leucocyte recruitment. An abnormal local vascular stromal environment can therefore influence local endothelial function and drive the persistence of local vascular inflammation. However, such local vascular inflammation can have distant effects on the systemic vascular system, leading to widespread endothelial cell dysfunction. Vascular endothelial dysfunction is common in a range of immune-mediated inflammatory diseases, is seen in multiple vascular beds, and is reversible following the induction of disease remission. The mechanisms that drive such systemic vascular endothelial dysfunction are unclear but factors such as TNF-alpha and CRP may play a role. Persistence of such widespread endothelial dysfunction in systemic vasculitis appears to have long-term consequences, leading to the acceleration of atherosclerosis and premature ischaemic heart disease. It may also underlie the accelerated atherosclerosis seen in other immune-mediated rheumatic diseases, such as rheumatoid arthritis.
authors.affiliation: Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, UK. c.d.buckley@bham.ac.uk
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
authors.forename: G Ed
authors.initials: GE
authors.lastname: Rainger
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Nash
authors.forename: Karim
authors.initials: K
authors.lastname: Raza
mesh_terms: D002450:Cell Communication; D042783:Endothelial Cells / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D017154:Stromal Cells / Q000502:physiology; D014657:Vasculitis / Q000503:physiopathology*