Imatinib inhibits vascular smooth muscle proteoglycan synthesis and reduces LDL binding in vitro and aortic lipid deposition in vivo

Mandy L Ballinger, Narin Osman, Kazuhiko Hashimura, Judy Bettina De Haan, Karin A Jandeleit-Dahm, Terri A Ilen, Lisa Tannock, John C Rutledge, Peter J Little

Research output: Contribution to journalArticleResearchpeer-review

46 Citations (Scopus)

Abstract

The `response to retention hypothesis of atherogenesis proposes that proteoglycans bind and retain low-density lipoproteins (LDL) in the vessel wall. Platelet-derived growth factor (PDGF) is strongly implicated in atherosclerosis and stimulates proteoglycan synthesis. Here we investigated the action of the PDGF receptor inhibitor imatinib on PDGF-mediated proteoglycan biosynthesis in vitro, lipid deposition in the aortic wall in vivo and the carotid artery ex vivo. In human vSMCs, imatinib inhibited PDGF mediated 35S-SO4 incorporation into proteoglycans by 31 (P <0.01) and inhibited PDGF-mediated size increases in both chemically cleaved and xyloside associated glycosaminoglycan (GAG) chains by 19 , P <0.05 and 27 , P <0.05, respectively.
Original languageEnglish
Pages (from-to)1408 - 1418
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume14
Issue number6B
DOIs
Publication statusPublished - 2010

Cite this