In the aortic wall of mammalian species, the maturation phase of smooth muscle cell (SMC) lineage is characterized by two temporally correlated but opposite regulatory processes of gene expression: upregulation of SM type SM2 myosin isoform and downregulation of brain (myosin heavy chain B)- and platelet (myosin heavy chain A(pla))-type nonmuscle myosins. Using the myosin isoform approach to study vascular SMC biology, we have shown (1) a marked SMC heterogeneity in adult arterial vessels, ie, coexistence of an "immature" and a fully differentiated SMC population; and (2) the propensity of the immature type SMC population to be activated in experimental models and human vascular diseases that are characterized by proliferation and migration of medial SMCs into the subendothelial space.