Abstract
Rabbit smooth muscle contains at least three types of myosin heavy chain (MHC) isoforms; SM1, SM2 and SMemb. SM1 and SM2 are specific to smooth muscle, but SMemb is a nonmuscle-type MHC abundantly expressed in the embryonic aorta. These three MHC isoforms are differentially expressed in the rabbit during normal vascular development and in experimental arterio- and atherosclerosis. This study investigated whether expression of human smooth muscle MHC isoforms is regulated in developing arteries and in atherosclerotic lesions. To accomplish this cDNA clones encoding human SM 1, SM2 and SMemb were isolated. The expression of SM2 mRNA in the fetal aorta was significantly lower compared to SM1 mRNA, but ratio of SM2- to SM1-mRNA in the aorta decreased after birth, but appeared to increase in the aged. In immunohistological studies using three antibodies against human MHC isoforms, SM1 was constitutively positive from the fetal stage to adulthood in the apparently normal media of the aorta and coronary arteries, whereas SM2 was negative in fetal arteries at an early gestational stage. In the human aorta or coronary arteries, unlike the rabbit, SMemb was detected even in the adult. Diffuse intimal thickening in the major coronary arteries was composed of smooth muscle cells, reacting equally to three antibodies for MHC isoforms, but reactivities with anti-SM2 antibody were reduced with aging. With progression of atherosclerosis, intimal smooth muscle diminished the expression of not only SM2 but also SM1, whereas α-smooth muscle actin was preserved. These results suggest that smooth muscle MHC isoforms are important molecular markers for studying human vascular smooth muscle cell differentiation as well as the cellular mechanisisms of atherosclerosis.
