{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T03:02:05Z","timestamp":1768791725856,"version":"3.49.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Treatment of occluded vessels can involve angioplasty, stenting, and bypass grafting, which can be limited by restenosis and thrombosis. Drug-eluting stents attenuate restenosis, but the current drugs used are cytotoxic, causing smooth muscle cell (SMC) and endothelial cell (EC) death that may lead to late thrombosis. N-cadherin is a junctional protein expressed by SMCs, which promotes directional SMC migration contributing to restenosis. We propose that engaging N-cadherin with mimetic peptides can act as a cell type\u2013selective therapeutic strategy to inhibit polarization and directional migration of SMCs without negatively impacting ECs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We designed a novel N-cadherin\u2013targeting chimeric peptide with a histidine-alanine-valine cadherin-binding motif, combined with a fibronectin-binding motif from\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              . This peptide was tested in SMC and EC culture assays of migration, viability, and apoptosis. Rat carotid arteries were balloon injured and treated with the N-cadherin peptide.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>Treating scratch-wounded SMCs with the N-cadherin\u2013targeting peptide inhibited migration and reduced polarization of wound-edge cells. The peptide colocalized with fibronectin. Importantly, EC junction, permeability, or migration was not impacted by peptide treatment in vitro. We also demonstrated that the chimeric peptide persisted for 24 hours after transient delivery in the balloon-injured rat carotid artery. Treatment with the N-cadherin\u2013targeting chimeric peptide reduced intimal thickening in balloon-injured rat carotid arteries at 1 and 2 weeks after injury. Reendothelialization of injured vessels after 2 weeks was unimpaired by peptide treatment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>These studies show that an N-cadherin\u2013binding and fibronectin-binding chimeric peptide is effective in inhibiting SMC migration in vitro and in vivo and limiting neointimal hyperplasia after balloon angioplasty without affecting EC repair. These results establish the potential of an advantageous SMC-selective strategy for antirestenosis therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.123.319400","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T09:00:22Z","timestamp":1688634022000},"page":"1639-1652","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Matrix-Binding, N-Cadherin\u2013Targeting Chimeric Peptide Inhibits Intimal Thickening but Not Endothelial Repair in Balloon-Injured Carotid Arteries"],"prefix":"10.1161","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3399-3339","authenticated-orcid":true,"given":"Jonah","family":"Burke-Kleinman","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine (J.B.-K., G.H., M.P.B.), University of Toronto, Canada."},{"name":"Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Canada (J.B.-K., J.R., G.H., J.P.S., M.P.B.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2897-418X","authenticated-orcid":true,"given":"Jonathan","family":"Rubianto","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering (J.R., J.P.S.), University of Toronto, Canada."},{"name":"Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Canada (J.B.-K., J.R., G.H., J.P.S., M.P.B.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangpei","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine (J.B.-K., G.H., M.P.B.), University of Toronto, Canada."},{"name":"Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Canada (J.B.-K., J.R., G.H., J.P.S., M.P.B.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3373-6463","authenticated-orcid":true,"given":"J. 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