Bolus endovascular PDGFR-beta antisense treatment suppressed intimal hyperplasia in a rat carotid injury model.

Abstract

BACKGROUND:

Intimal thickening in accelerated arteriopathies relies on the migration of medial vascular smooth muscle cells (VSMCs) and their proliferation within the neointima. Activation of platelet-derived growth factor receptor-beta (PDGFR-beta) expressed in injured VSMCs is responsible for the migration of medial VSMCs to the intima. In the present study, we wanted to assess whether a single local endovascular delivery of antisense PDGFR-beta in injured rat carotid arteries would be sufficient to prevent intimal hyperplasia and how it might contribute to the vascular healing process.

METHODS AND RESULTS:

A bolus of antisense PDGFR-beta delivered into injured rat carotid arteries reduced PDGFR-beta protein overexpression by >90% from day 3 to 28 after injury. At day 28 after injury, compared with injured untreated carotids, treatment with antisense PDGFR-beta reduced intimal hyperplasia by 58% and medial VSMC migration by 49% and improved vascular reendothelialization by 100% and vascular reactivity (EC(50)) to acetylcholine by 5-fold.

CONCLUSIONS:

A single-bolus luminal delivery of antisense PDGFR-beta to injured rat carotids reduced intimal hyperplasia, improved the reendothelialization process, and led to the recovery of endothelium-dependent regulation of vascular tone.

• Authors: N Noiseux, C H Boucher, R Cartier, M G Sirois
• Journal: Circulation (Circulation) Vol. 102 Issue 11 Pg. 1330-6 (Sep 12 2000) ISSN: 1524-4539 [Electronic] United States
• PMID: 10982551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oligonucleotides, Antisense
• Receptor, Platelet-Derived Growth Factor beta

Topics

• Animals
• Carotid Artery Diseases (pathology)
• Carotid Artery, Common (metabolism, pathology, physiopathology)
• Cell Count
• Cell Division
• Endothelium, Vascular (metabolism, pathology)
• Hyperplasia
• Immunohistochemistry
• In Vitro Techniques
• Infusions, Intra-Arterial
• Male
• Muscle Contraction
• Oligonucleotides, Antisense (administration & dosage, chemistry, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Platelet-Derived Growth Factor beta (chemistry, metabolism)
• Tunica Intima (metabolism, pathology)
• Tunica Media (metabolism, pathology)