Inflammation and immune system contribution to the etiology of atherosclerosis: mechanisms and methods of assessment.

Abstract

Immune system activation and inflammation are intricately involved in the development and progression of atherosclerosis. The purposes of this review are to (a) discuss effects of inflammation and the immune system across the lifespan of atherosclerotic plaque, (b) review current recommended testing techniques for assessing inflammation using blood and within the atherosclerotic plaque, and (c) link basic research in inflammation and immunology with ongoing clinical research with potential to impact prevention and treatment interventions in atherosclerotic disease. The atherosclerotic process is typically initiated in the presence of endothelial dysfunction by increased uptake, entrapment, and deposition of lipids, especially low-density lipoprotein (LDL). Once inside the intima, LDL can become oxidized (LDLox), which promotes further endothelial cell activation/injury, stimulates adhesion molecule expression, and releases chemotactic factors that promote leukocyte-endothelial interactions. The process of atherogenesis is highly regulated by the innate and adaptive immune systems and systemic inflammatory response. In addition, proinflammatory mediators play a key role in the lifespan of the atherosclerotic plaque and its vulnerability, favoring eventual plaque fissure when exposed to increasing hemodynamic stress. The complex atherosclerotic process involves the innate and adaptive immune systems and systemic inflammatory activation. Incorporation of advances in understanding inflammation and immune system contributions to the etiology of atherosclerosis into intervention research allows the development of novel approaches to prevention and treatment.