Impaired vascular contractility and blood pressure homeostasis in the smooth muscle α-actin null mouse

Lisa A. Schildmeyer, Renee Braun, George Taffet, Mariella Debiasi, Alan E. Burns, Allan Bradley, Robert J. Schwartz

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

Abstract

The smooth muscle (SM) α-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 α-actins. SM α-actin also appears during vascular development, but becomes the single most abundant protein in adult vascular smooth muscle cells. Tissue-specific expression of SM α-actin is thought to be required for the principal force-generating capacity of the vascular smooth muscle cell. We wanted to determine whether SM α-actin gene expression actually relates to an actin isoform's function. Analysis of SM α-actin null mice indicated that SM α-actin is not required for the formation of the cardiovascular system. Also, SM α-actin null mice appeared to have no difficulty feeding or reproducing. Survival in the absence of SM α-actin may result from other actin isoforms partially substituting for this isoform. In fact, skeletal α-actin gene, an actin isoform not usually expressed in vascular smooth muscle, was activated in the aortas of these SM α-actin null mice. However, even with a modest increase in skeletal α-actin activity, highly compromised vascular contractility, tone, and blood flow were detected in SM α-actin-defective mice. This study supports the concept that SM α-actin has a central role in regulating vascular contractility and blood pressure homeostasis, but is not required for the formation of the cardiovascular system.

Original languageEnglish (US)
Pages (from-to)2213-2220
Number of pages8
JournalFASEB Journal
Volume14
Issue number14
DOIs
StatePublished - 2000

Keywords

  • Homologous recombination
  • SM α-actin gene
  • Vascular tone

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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