Inhibition of Vascular Smooth Muscle Cell Migration and Intimal Thickening with Chimeric N-Cadherin Mimetic Peptides: Development of a Novel Therapeutic Strategy for Restenosis

Heart disease is the foremost cause of global mortality and involves the blockage of arteries. The most common treatment for this is angioplasty and stenting, which has side effects of restenosis (re-narrowing) from smooth muscle cell (SMC) migration and proliferation, and late thrombosis due to endothelial cell (EC) death from indiscriminately cytotoxic chemotherapeutic agents. We developed a chimeric peptide with a mimetic domain for neural (N)-cadherin and a matrix- anchoring domain which binds fibronectin that can be delivered to injured blood vessels to inhibit SMC migration while allowing EC regeneration. This N-cadherin mimetic peptide (NCad peptide) inhibited the migration of rodent and human SMCs, but did not inhibit migration or viability of ECs, and did not induce inflammation or permeabilization of the EC barrier. The NCad peptide is combined with biocompatible nanoparticles and coated onto balloon catheters, comprising a potential therapeutic strategy for the prevention of restenosis and thrombosis after angioplasty.

Department dc:contributor.department

Laboratory Medicine and Pathobiology

Year dc:date.issued

2024

Author dc:creator

• Burke-Kleinman, Jonah

Advisors dc:contributor.advisor

• Bendeck, Michelle P
• Santerre, J Paul

• Angioplasty
• Atherosclerosis
• Cardiovascular
• N-cadherin
• Restenosis

Statement dc:rights

• Attribution-NonCommercial-NoDerivatives 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/4.0/

Handle dc:identifier.uri

http://hdl.handle.net/1807/140174

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/140174