Atherosclerosis: from lesion formation to plaque activation and endothelial dysfunction.

Atherosclerosis is an important source of morbidity and mortality in the developed world. Despite the fact that the association between LDL cholesterol and atherosclerosis has been evident for at least three decades, our understanding of exactly how LDL precipitates atherosclerosis is still in its infancy. At least three working hypotheses of atherosclerosis are now nearing the stage where their critical evaluation is possible through a combination of basic science investigation and murine models of atherosclerosis. As we move forward in our understanding of this disease, efforts will be increasingly focused on the molecular mechanisms of disease activation that precipitate the clinical manifestations of atherosclerosis such as heart attack and stroke. Two candidates for such investigation involve the events surrounding plaque activation and endothelial dysfunction. Further investigation in these fields should provide the necessary insight to develop the next generation of interventions that will reduce the clinical manifestations of this devastating disease. The purpose of this work is to review the major theories of atherogenesis, examine the aspects of atherosclerosis that lead to disease activation and discuss aspects of disease activation that are amenable to treatment.