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Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells.

Publication ,  Journal Article
Naftilan, AJ; Pratt, RE; Dzau, VJ
Published in: J Clin Invest
April 1989

Recently, angiotensin II (Ang II) has been shown to cause hypertrophy of cultured quiescent rat aortic smooth muscle (RASM) cells. This observation along with the demonstration of angiotensinogen mRNA in the vessel wall has led us to postulate a role for vascular angiotensin in hypertensive blood vessel hypertrophy. To investigate further the possible molecular mechanisms, we examined the effect of Ang II on the expression of two genes known to be involved with cellular growth response. Near-confluent RASM cells were made quiescent by 48-h exposure to a defined serum-free medium. Ang II (10(-6) to 10(-11) M) resulted in an induction of the protooncogene c-myc mRNA within 30 min which persisted for 6 h. Interestingly, 6 h after the addition of Ang II, platelet-derived growth factor (PDGF) A-chain mRNA expression was elevated, peaked in 9 h, and persisted for 11 h. This was accompanied with a 15-20-fold increase in PDGF concentration in the culture medium. These effects were dose-dependent and were blocked by saralasin. Whereas the inhibition of protein synthesis by cycloheximide resulted in a stabilization of c-myc mRNA, cycloheximide abolished the elevation of the PDGF A-chain mRNA. Taken together, our data show that exposure of RASM cells to Ang II results in the sequential activation of c-myc and PDGF A-chain mRNA expressions. This sequential activation of protooncogene and growth factor gene may be an important mechanism in angiotensin-induced smooth muscle growth and hypertrophy.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

April 1989

Volume

83

Issue

4

Start / End Page

1419 / 1424

Location

United States

Related Subject Headings

  • Rats
  • RNA, Messenger
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Proteins
  • Platelet-Derived Growth Factor
  • Oncogenes
  • Muscle, Smooth, Vascular
  • Immunology
  • Gene Expression Regulation
  • Cells, Cultured
 

Citation

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Naftilan, A. J., Pratt, R. E., & Dzau, V. J. (1989). Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells. J Clin Invest, 83(4), 1419–1424. https://doi.org/10.1172/JCI114032
Naftilan, A. J., R. E. Pratt, and V. J. Dzau. “Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells.J Clin Invest 83, no. 4 (April 1989): 1419–24. https://doi.org/10.1172/JCI114032.
Naftilan, A. J., et al. “Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells.J Clin Invest, vol. 83, no. 4, Apr. 1989, pp. 1419–24. Pubmed, doi:10.1172/JCI114032.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

April 1989

Volume

83

Issue

4

Start / End Page

1419 / 1424

Location

United States

Related Subject Headings

  • Rats
  • RNA, Messenger
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Proteins
  • Platelet-Derived Growth Factor
  • Oncogenes
  • Muscle, Smooth, Vascular
  • Immunology
  • Gene Expression Regulation
  • Cells, Cultured