title: The vascular smooth muscle alpha-actin gene is reactivated during cardiac hypertrophy provoked by load.
abstract: Cardiac hypertrophy triggered by mechanical load possesses features in common with growth factor signal transduction. A hemodynamic load provokes rapid expression of the growth factor-inducible nuclear oncogene, c-fos, and certain peptide growth factors specifically stimulate the "fetal" cardiac genes associated with hypertrophy, even in the absence of load. These include the gene encoding vascular smooth muscle alpha-actin, the earliest alpha-actin expressed during cardiac myogenesis; however, it is not known whether reactivation of the smooth muscle alpha-actin gene occurs in ventricular hypertrophy. We therefore investigated myocardial expression of the smooth muscle alpha-actin gene after hemodynamic overload. Smooth muscle alpha-actin mRNA was discernible 24 h after coarctation and was persistently expressed for up to 30 d. In hypertrophied hearts, the prevalence of smooth muscle alpha-actin gene induction was 0.909, versus 0.545 for skeletal muscle alpha-actin (P less than 0.05). Ventricular mass after 2 d or more of aortic constriction was more highly correlated with smooth muscle alpha-actin gene activation (r = 0.852; P = 0.0001) than with skeletal muscle alpha-actin (r = 0.532; P = 0.009); P less than 0.0005 for the difference in the correlation coefficients. Thus, smooth muscle alpha-actin is a molecular marker of the presence and extent of pressure-overload hypertrophy, whose correlation with cardiac growth at least equals that of skeletal alpha-actin. Induction of smooth muscle alpha-actin was delayed and sustained after aortic constriction, whereas the nuclear oncogenes c-jun and junB were expressed rapidly and transiently, providing potential dimerization partners for transcriptional control by c-fos.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: F M
authors.initials: FM
authors.lastname: Black
authors.forename: S E
authors.initials: SE
authors.lastname: Packer
authors.forename: T G
authors.initials: TG
authors.lastname: Parker
authors.forename: L H
authors.initials: LH
authors.lastname: Michael
authors.forename: R
authors.initials: R
authors.lastname: Roberts
authors.forename: R J
authors.initials: RJ
authors.lastname: Schwartz
authors.forename: M D
authors.initials: MD
authors.lastname: Schneider
mesh_terms: D000199:Actins / Q000235:genetics*; D000818:Animals; D001017:Aortic Coarctation / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism; D005786:Gene Expression Regulation; D016762:Genes, fos; D016758:Genes, jun; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015533:Transcriptional Activation
chemical_list: D000199:Actins; D012333:RNA, Messenger