Fibroblast activation in vascular inflammation

Vascular inflammation is implicated in both local and systemic inflammatory conditions. Endothelial activation and leukocyte extravasation are key events in vascular inflammation. Lately, the role of the stromal microenvironment as a source of proinflammatory stimuli has become increasingly appreciated. Stromal fibroblasts produce cytokines, growth factors and proteases that trigger and maintain acute and chronic inflammatory conditions. Fibroblasts have been associated with connective tissue pathologies such as scar formation and fibrosis, but recent research has also connected them with vascular dysfunctions. Fibroblasts are able to modulate endothelial cell functions in a paracrine manner, including proinflammatory activation and promotion of angiogenesis. They are also able to activate and attract leukocytes. Stromal fibroblasts can thus cause a proinflammatory switch in endothelial cells, and promote leukocyte infiltration into tissues. New insights in the role of adventitial fibroblasts have further strengthened the link between stromal fibroblasts and proinflammatory vascular functions. This review focuses on the role of fibroblasts in inducing and maintaining vascular inflammation, and describes recent findings and concepts in the field, along with examples of pathologic implications.