ABSTRACT
The clinical repercussions of atherosclerosis – myocardial infarction (MI), chronic angina pectoris, sudden arrhythmic death, stroke, peripheral vascular disease, renal artery stenosis – offer an incomplete portrait of the devastating consequences of this common disease. Atherosclerosis stands as the primary cause of death and disability in the developed world, and has thus engendered extensive scrutiny through many different forms of research and study. Despite this focused attention, enduring gaps of understanding persist even in the face of major scientific and therapeutic advances that have reshaped the practice of cardiology. Such limitations derive in large part from the complex and contrasting forces at work in atherosclerosis. Atherosclerosis is a chronic disorder that develops over decades, yet its most serious sequelae, e.g. MI and sudden death, often occur in minutes. Although present in the young, atherosclerosis typically becomes manifest in the middle-aged or elderly. Multiple risk factors – hypertension, smoking, obesity, diabetes mellitus, dyslipidemia – promote atherosclerosis, but any one of these risk factors alone can induce the disease in some individuals. The disease itself is a nexus of pathology that integrates lipid metabolism and transport, oxidative reactions, thrombosis, and inflammation. As a result, the cellular protagonists range from structural arterial cells like endothelial cells and vascular smooth muscle cells to invading inflammatory cells (lymphocytes and monocytes) and circulating elements (platelets). These cells signal and respond to one another through a myriad of extracellular proteins and intracellular messengers.
