Cholesterol, cytokines and atherosclerosis

Atherosclerosis is a chronic inflammatory response of the vascular wall to endothelial injury or dysfunction. Over the last several decades, basic and clinical cardiovascular research has significantly enhanced our understanding of pathophysiological processes leading to formation, progression, and complications of atherosclerotic plaques. Atherosclerosis starts with an innate immune response involving the recruitment and activation of monocytes ⁄ macrophages that respond to an excessive accumulation of modified lipids within the arterial wall, followed by an adaptive immune response involving antigen-specific T lymphocytes. Monocyte/macrophage recruitment by abnormal endothelium over developing atherosclerotic plaques, is aided by endothelial expression of adhesion molecules (selectins, ICAM-1, VCAM, ELAM). The accumulation of inflammatory cells within the arterial wall leads to local production of chemokines, interleukins and proteases that enhance the influx of monocytes and lymphocytes, thereby promoting the progression of atherosclerotic lesions. Also macrophages play important roles in the progression of atherosclerosis by exhibiting unique characteristics under the various stimuli, evolving the plaque instability, thrombus formation and remodeling. Experimental atherosclerosis in animals furnishes an important research tool, but extrapolation to humans requires care. Understanding how to combine experimental and clinical science will provide further insight into atherosclerosis. The knowledge of atherosclerosis as an inflammatory disease offers the opportunity to develop novel therapeutic strategies targeting the inflammatory component of the disease.