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In vivo gene transfer of dominant-negative rho-kinase induces regression of coronary arteriosclerosis in pigs.

K Morishige1, H Shimokawa, Y Eto

  • 1Department of Cardiovascular Medicine, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan.

Annals of the New York Academy of Sciences
|January 25, 2002
PubMed
Summary

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Adenovirus-mediated transfer of dominant-negative Rho-kinase (AdDNRhoK) reversed coronary arteriosclerosis in a pig model. This inhibition of Rho-kinase effectively reduced arterial constriction and vasospasm, offering a potential therapeutic strategy.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Vascular Pathophysiology

Background:

  • Small GTPase Rho and Rho-kinase are implicated in arteriosclerosis pathogenesis.
  • Rho-kinase regulates cellular functions relevant to vascular remodeling and contractility.

Purpose of the Study:

  • To investigate the therapeutic potential of inhibiting Rho-kinase in a porcine model of coronary arteriosclerosis.
  • To determine if dominant-negative Rho-kinase can reverse existing constrictive remodeling and vasospasm.

Main Methods:

  • Induction of coronary constrictive remodeling and vasospasm using interleukin-1,beta in porcine coronary segments.
  • Adenovirus-mediated gene transfer of dominant-negative Rho-kinase (AdDNRhoK) or beta-galactosidase.
  • Assessment of coronary remodeling, vasospastic activity, and Rho-kinase target protein phosphorylation.

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Last Updated: Jul 12, 2026

Gene Transfer for Ischemic Heart Failure in a Preclinical Model
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In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium
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Large Animal Model for Evaluating the Efficacy of the Gene Therapy in Ischemic Heart
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Main Results:

  • AdDNRhoK treatment led to regression of coronary constrictive remodeling and abolished vasospastic responses to serotonin.
  • Control treatment with beta-galactosidase did not reverse the observed pathological changes.
  • Unregulated phosphorylation of Rho-kinase target proteins in coronary lesions was significantly suppressed by AdDNRhoK.

Conclusions:

  • Rho-kinase plays a substantial role in the mechanism of coronary arteriosclerosis.
  • Selective inhibition of Rho-kinase, as demonstrated by AdDNRhoK, can reverse established coronary arteriosclerosis in a relevant in vivo model.