Intimal Smooth Muscle Cells

“Know the enemy and know yourself; in numerous battles you will never be in peril.” Sun Tzu ( The Art of War , Chapter III)The sixth-century BC Chinese military general Sun Tzu underscored the dangers of overconfidence in strategy. A similar view has been shared by other thinkers and applied further to various contexts other than the military. A major goal of the medical sciences is to develop effective, well-refined therapies. Accomplishing this task requires a comprehensive understanding of the biology of each component in the disease mechanism and realization of the limits of current knowledge. This view can apply not only to the development of new therapies but also to advanced diagnostics (eg, imaging and biomarkers).Article see p 2048The biology of vascular smooth muscle cells (SMC) has been central to cardiovascular research. Many investigations have focused on the mechanisms of SMC accumulation in the tunica intima, an inner layer of the vessel wall between the endothelium and the media. Evidence suggests that, unlike arteries in other mammals, those in humans spontaneously develop intima of substantial thickness. In addition to higher cholesterol levels (even in normolipidemic individuals compared with other mammals) and other human-specific risk factors (eg, smoking), the intima may serve as a soil for the future development of atherosclerotic plaques.1 Coronary atherosclerosis leads to acute thrombotic complications, the leading cause of death in many countries.High plasticity represents a unique feature of SMC compared with other muscle cell types. A classic theory proposes that, on activation in response to injury or inflammatory stimuli, medial SMC migrate into the subendothelial space, proliferate, and produce extracellular matrix, forming the tunica intima. Once relocated to the intima, migrated SMC regain a quiescent phenotype over time.2,3 This phenomenon suggests that SMC can transiently modulate their phenotype, …