Cytokines as mediators of vascular pathology

Abstract

Interactions between leukocytes and intrinsic vascular wall cells characterize many inflammatory reactions and contribute importantly to the pathogenesis of many vascular diseases. In view of this intimate involvement of leukocytes in vascular pathology it is important to understand the signals that recruit and activate leukocytes locally in regions of vascular pathology. It is also desirable to delineate the mechanisms by which leukocytes influence the behavior of intrinsic vascular wall cells in ways which may contribute to vascular lesion formation. Mediators elaborated by leukocytes include small molecules including lipid-derived mediators such as prostanoids, leukotrienes, and platelet activating factor. Leukocytes can also produce protein mediators including those currently classified as cytokines. The cytokines, protein mediators involved in inflammation and control of the immune response, derive from all classes of leukocytes studied. Local cytokine networks may orchestrate complex programs of expression of functions of leukocytes and endothelial and smooth muscle cells involved in vascular homeostasis and pathology. Our laboratory has been interested in hyperplastic arterial diseases including atherosclerosis and restenosis following angioplasty treatment of obstructive atherosclerosis. Definitive evidence for roles of cytokines in the pathogenesis of these syndromes are lacking. However, various in vitro and in vivo studies have furnished sufficient information to permit formulation of rather detailed hypotheses or models. In hypercholesterolemic rabbits vascular cell adhesion molecule-l (VCAM-l) may participate in initial monocyte recruitment to prelesional areas of arterial endothelium. Other adhesion molecules including Intercellular adhesion molecule-l (ICAM-l) may also participate in monocyte adhesion to arterial endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)