title: Impaired vascular contractility and blood pressure homeostasis in the smooth muscle alpha-actin null mouse.
abstract: The smooth muscle (SM) alpha-actin gene activated during the early stages of embryonic cardiovascular development is switched off in late stage heart tissue and replaced by cardiac and skeletal alpha-actins. SM alpha-actin also appears during vascular development, but becomes the single most abundant protein in adult vascular smooth muscle cells. Tissue-specific expression of SM alpha-actin is thought to be required for the principal force-generating capacity of the vascular smooth muscle cell. We wanted to determine whether SM alpha-actin gene expression actually relates to an actin isoform's function. Analysis of SM alpha-actin null mice indicated that SM alpha-actin is not required for the formation of the cardiovascular system. Also, SM alpha-actin null mice appeared to have no difficulty feeding or reproducing. Survival in the absence of SM alpha-actin may result from other actin isoforms partially substituting for this isoform. In fact, skeletal alpha-actin gene, an actin isoform not usually expressed in vascular smooth muscle, was activated in the aortas of these SM alpha-actin null mice. However, even with a modest increase in skeletal alpha-actin activity, highly compromised vascular contractility, tone, and blood flow were detected in SM alpha-actin-defective mice. This study supports the concept that SM alpha-actin has a central role in regulating vascular contractility and blood pressure homeostasis, but is not required for the formation of the cardiovascular system.
authors.affiliation: Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Department of Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Schildmeyer
authors.forename: R
authors.initials: R
authors.lastname: Braun
authors.forename: G
authors.initials: G
authors.lastname: Taffet
authors.forename: M
authors.initials: M
authors.lastname: Debiasi
authors.forename: A E
authors.initials: AE
authors.lastname: Burns
authors.forename: A
authors.initials: A
authors.lastname: Bradley
authors.forename: R J
authors.initials: RJ
authors.lastname: Schwartz
mesh_terms: D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology*; D015152:Blotting, Northern; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000199:Actins; D012333:RNA, Messenger