Modulation of the inflammatory response in cardiovascular disease.

Abstract

There is a growing body of evidence that inflammation might play an important role in the initiation and progression of cardiovascular diseases (CVDs). The designation of CVD as a chronic inflammatory process is further supported by evidence that the risk factors for CVD cause endothelial cells throughout the vascular tree to assume an inflammatory phenotype. These activated endothelial cells characteristically exhibit oxidative stress and increased adhesiveness for circulating leukocytes. Although initial efforts to define the mechanisms underlying the inflammatory phenotype in diseased endothelial cells have focused on the linkage between oxidative stress and adhesion molecule activation/expression, recent work has implicated a variety of additional factors that can modulate the magnitude and/or nature of the inflammatory responses in CVD. Platelets, angiotensin II, and the CD40/CD40 ligand signaling system are gaining recognition as contributors to the pathogenesis of CVD. These factors appear to converge with known pathways that link oxidative stress with adhesion molecule expression and help to explain the apparent integration of coagulation with inflammation in CVD. These factors also hold the promise of offering multiple sites for therapeutic intervention in CVD.