Smooth muscle phenotype in aortic diseases: Are there other histopathological markers besides contractile myofibrils?

More than 30 years ago, Campbell et al. (1) published their classical paper on phenotypic changes in arterial smooth muscle cell (SMC) populations. This has developed into a highly useful concept explaining arterial wall homeostasis or pathogenesis of many arterial diseases. Vascular SMCs occur between two extreme phenotypes. The synthetic phenotype is responsible for producing most of the vascular extracellular matrix, including collagen, elastin, and glycosaminoglycans, of the ground substance during ontogenesis and growth. Under normal conditions, it gradually differentiates into the contractile phenotype with abundant actin, myosin, and desmin myofibrils, which provide mechanical support even in large elastic arteries. However, under pathological conditions such as atherosclerosis or any other arterial inflammatory disease, mechanical damage, or hypertension (2), cells switch back from the contractile to synthetic phenotype, which often possesses migratory and proliferative capabilities as well. According to our current understanding, this is a hallmark of the progression of atherosclerosis and vascular stenosis (3). The vascular SMC phenotype became a part of the histological classification of atherosclerosis (4) as well as important for assessing the vulnerability of arterial wall, a concept developed and well established in the laboratory of Renu Virmani as recently summarized by Kolodgie et al. (5).