Myocyte enhancer binding factor-2 expression and activity in vascular smooth muscle cells

Association with the activated phenotype

Anthony Firulli, Joseph M. Miano, Weizhen Bi, A. Daniel Johnson, Ward Casscells, Eric N. Olson, John J. Schwarz

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Proliferation and phenotypic modulation of smooth muscle cells (SMCs) are major components of the vessel's response to injury in experimental models of restenosis. Some of the growth factors involved in restenosis have been identified, but to date little is known about the transcription factors that ultimately regulate this process. We examined the expression of the four members of the myocyte enhancer binding factor-2 (MEF2) family of transcription factors in cultured rat aortic SMCs (RASMCs) and a rat model of restenosis because of their known importance in regulating the differentiated phenotype of skeletal and cardiac muscle. In skeletal and cardiac muscle, the MEF2s are believed to be important for activating the expression of contractile protein and other muscle-specific genes. Therefore, we anticipated that the MEF2s would be expressed at high levels in medial SMCs that are producing contractile proteins and that they would be downregulated along with the contractile protein genes in neointimal SMCs. On the contrary, we observe that MEF2A, MEF2B, and MEF2D mRNAs are upregulated in the neointima, with the highest levels in the layer of cells nearest to the lumen, whereas MEF2C mRNA levels do not appreciably increase. Moreover, few cells in the media are making MEF2 proteins detectable by immunohistochemistry, whereas large number of neointimal cells are positive for all four MEF2s. These data suggest that the MEF2s are involved in the activated smooth muscle phenotype and not in the maintenance of contractile protein gene expression.

Original languageEnglish (US)
Pages (from-to)196-204
Number of pages9
JournalCirculation Research
Volume78
Issue number2
StatePublished - Feb 1996
Externally publishedYes

Fingerprint

MEF2 Transcription Factors
Contractile Proteins
Vascular Smooth Muscle
Smooth Muscle Myocytes
Phenotype
Myocardium
Skeletal Muscle
Transcription Factors
Neointima
Messenger RNA
Cellular Structures
Genes
Smooth Muscle
Intercellular Signaling Peptides and Proteins
Theoretical Models
Down-Regulation
Cell Count
Immunohistochemistry
Maintenance
Gene Expression

Keywords

  • balloon injury
  • MEF2
  • mRNA
  • smooth muscle
  • transcription factor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Firulli, A., Miano, J. M., Bi, W., Johnson, A. D., Casscells, W., Olson, E. N., & Schwarz, J. J. (1996). Myocyte enhancer binding factor-2 expression and activity in vascular smooth muscle cells: Association with the activated phenotype. Circulation Research, 78(2), 196-204.

Myocyte enhancer binding factor-2 expression and activity in vascular smooth muscle cells : Association with the activated phenotype. / Firulli, Anthony; Miano, Joseph M.; Bi, Weizhen; Johnson, A. Daniel; Casscells, Ward; Olson, Eric N.; Schwarz, John J.

In: Circulation Research, Vol. 78, No. 2, 02.1996, p. 196-204.

Research output: Contribution to journalArticle

Firulli, A, Miano, JM, Bi, W, Johnson, AD, Casscells, W, Olson, EN & Schwarz, JJ 1996, 'Myocyte enhancer binding factor-2 expression and activity in vascular smooth muscle cells: Association with the activated phenotype', Circulation Research, vol. 78, no. 2, pp. 196-204.
Firulli, Anthony ; Miano, Joseph M. ; Bi, Weizhen ; Johnson, A. Daniel ; Casscells, Ward ; Olson, Eric N. ; Schwarz, John J. / Myocyte enhancer binding factor-2 expression and activity in vascular smooth muscle cells : Association with the activated phenotype. In: Circulation Research. 1996 ; Vol. 78, No. 2. pp. 196-204.
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