Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI117402

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

R Morishita, G H Gibbons, R E Pratt, N Tomita, Y Kaneda, T Ogihara, and V J Dzau

Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94035.

Find articles by Morishita, R. in: PubMed | Google Scholar

Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94035.

Find articles by Gibbons, G. in: PubMed | Google Scholar

Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94035.

Find articles by Pratt, R. in: PubMed | Google Scholar

Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94035.

Find articles by Tomita, N. in: PubMed | Google Scholar

Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94035.

Find articles by Kaneda, Y. in: PubMed | Google Scholar

Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94035.

Find articles by Ogihara, T. in: PubMed | Google Scholar

Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94035.

Find articles by Dzau, V. in: PubMed | Google Scholar

Published August 1, 1994 - More info

Published in Volume 94, Issue 2 on August 1, 1994
J Clin Invest. 1994;94(2):824–829. https://doi.org/10.1172/JCI117402.
© 1994 The American Society for Clinical Investigation
Published August 1, 1994 - Version history
View PDF
Abstract

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.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 824
page 824
icon of scanned page 825
page 825
icon of scanned page 826
page 826
icon of scanned page 827
page 827
icon of scanned page 828
page 828
icon of scanned page 829
page 829
Version history
  • Version 1 (August 1, 1994): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts