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Autocrine and paracrine effects of atrial natriuretic peptide gene transfer on vascular smooth muscle and endothelial cellular growth.

Publication ,  Journal Article
Morishita, R; Gibbons, GH; Pratt, RE; Tomita, N; Kaneda, Y; Ogihara, T; Dzau, VJ
Published in: J Clin Invest
August 1994

In addition to the atria, recent evidence suggests that atrial natriuretic peptide (ANP) is also synthesized in other tissues. Of particular interest is the location of ANP mRNA in the vessel wall. We and others have shown that exogenously added ANP inhibited the growth of endothelial cells and vascular smooth muscle cells (VSMC) in culture. However, it is not known if the locally synthesized ANP would act similarly. Because cultured endothelial cells and VSMC have lost the ability to express the endogenous ANP gene, we have transfected cells in culture with an expression vector expressing rat ANP and have examined the effects on growth. Cultured endothelial cells transfected with an ANP expression vector synthesized and secreted high levels of ANP. These cells also showed significantly lower rates of DNA synthesis under basal and fibroblast growth factor (FGF)-stimulated conditions. Addition of conditioned medium from endothelial cells transfected with ANP vector to nontransfected endothelial cells resulted in the significant increase in cyclic GMP. Similarly, conditioned media collected from endothelial cells transfected with ANP vector also decreased DNA synthesis in VSMC. Coculture of ANP-transfected endothelial cells with quiescent VSMC showed that released ANP from endothelial cells inhibited DNA synthesis in VSMC. Finally, we examined the autocrine effect of direct transfection of ANP vector into VSMC. Transfection of the ANP vector decreased DNA synthesis in VSMC under basal and angiotensin II-stimulated conditions. Similarly, transfection of the ANP vector resulted in a decrease in the PDGF and serum (5%)-stimulated DNA synthesis of VSMC. These results demonstrate that endogenously produced ANP can exert autocrine and paracrine inhibitory effects on endothelial cell and VSMC growth. In vivo gene transfer of ANP may provide us with the opportunity of gene therapy for vascular diseases in which the abnormalities are vasoconstriction and pathological growth.

Duke Scholars

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

August 1994

Volume

94

Issue

2

Start / End Page

824 / 829

Location

United States

Related Subject Headings

  • Muscle, Smooth, Vascular
  • Immunology
  • Genetic Therapy
  • Gene Transfer Techniques
  • Endothelium, Vascular
  • DNA
  • Culture Media, Conditioned
  • Cells, Cultured
  • Cell Division
  • Cattle
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Morishita, R., Gibbons, G. H., Pratt, R. E., Tomita, N., Kaneda, Y., Ogihara, T., & Dzau, V. J. (1994). Autocrine and paracrine effects of atrial natriuretic peptide gene transfer on vascular smooth muscle and endothelial cellular growth. J Clin Invest, 94(2), 824–829. https://doi.org/10.1172/JCI117402
Morishita, R., G. H. Gibbons, R. E. Pratt, N. Tomita, Y. Kaneda, T. Ogihara, and V. J. Dzau. “Autocrine and paracrine effects of atrial natriuretic peptide gene transfer on vascular smooth muscle and endothelial cellular growth.J Clin Invest 94, no. 2 (August 1994): 824–29. https://doi.org/10.1172/JCI117402.
Morishita R, Gibbons GH, Pratt RE, Tomita N, Kaneda Y, Ogihara T, et al. Autocrine and paracrine effects of atrial natriuretic peptide gene transfer on vascular smooth muscle and endothelial cellular growth. J Clin Invest. 1994 Aug;94(2):824–9.
Morishita, R., et al. “Autocrine and paracrine effects of atrial natriuretic peptide gene transfer on vascular smooth muscle and endothelial cellular growth.J Clin Invest, vol. 94, no. 2, Aug. 1994, pp. 824–29. Pubmed, doi:10.1172/JCI117402.
Morishita R, Gibbons GH, Pratt RE, Tomita N, Kaneda Y, Ogihara T, Dzau VJ. Autocrine and paracrine effects of atrial natriuretic peptide gene transfer on vascular smooth muscle and endothelial cellular growth. J Clin Invest. 1994 Aug;94(2):824–829.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

August 1994

Volume

94

Issue

2

Start / End Page

824 / 829

Location

United States

Related Subject Headings

  • Muscle, Smooth, Vascular
  • Immunology
  • Genetic Therapy
  • Gene Transfer Techniques
  • Endothelium, Vascular
  • DNA
  • Culture Media, Conditioned
  • Cells, Cultured
  • Cell Division
  • Cattle