Affordable Access

Publisher Website

Down-regulation of Plasminogen Activator Inhibitor 1 Expression Promotes Myocardial Neovascularization by Bone Marrow Progenitors

Journal of Experimental Medicine
The Rockefeller University Press
Publication Date
DOI: 10.1084/jem.20040221
  • Article
  • Biology


Human adult bone marrow–derived endothelial progenitors, or angioblasts, induce neovascularization of infarcted myocardium via mechanisms involving both cell surface urokinase-type plasminogen activator, and interactions between β integrins and tissue vitronectin. Because each of these processes is regulated by plasminogen activator inhibitor (PAI)-1, we selectively down-regulated PAI-1 mRNA in the adult heart to examine the effects on postinfarct neovascularization and myocardial function. Sequence-specific catalytic DNA enzymes inhibited rat PAI-1 mRNA and protein expression in peri-infarct endothelium within 48 h of administration, and maintained down-regulation for at least 2 wk. PAI-1 inhibition enhanced vitronectin-dependent transendothelial migration of human bone marrow–derived CD34+ cells, and resulted in a striking augmentation of angioblast-dependent neovascularization. Development of large, thin-walled vessels at the peri-infarct region was accompanied by induction of proliferation and regeneration of endogenous cardiomyocytes and functional cardiac recovery. These results identify a causal relationship between elevated PAI-1 levels and poor outcome in patients with myocardial infarction through mechanisms that directly inhibit bone marrow–dependent neovascularization. Strategies that reduce myocardial PAI-1 expression appear capable of enhancing cardiac neovascularization, regeneration, and functional recovery after ischemic insult.

There are no comments yet on this publication. Be the first to share your thoughts.


Seen <100 times

More articles like this

Down-regulation of plasminogen activator inhibitor...

on Journal of Experimental Medici... Dec 20, 2004

Downregulated expression of plasminogen activator...

on Journal of the American Colleg... Aug 02, 2005

Downregulated Expression of Plasminogen Activator...

on Journal of the American Colleg... Jan 01, 2005

Dexamethasone-induced plasminogen activator inhibi...

on Biomedical research (Tokyo, Ja... October 2010
More articles like this..