Soluble N-Cadherin Overexpression Reduces Features of Atherosclerotic Plaque Instability

CA Lyon, JL Johnson, H Williams, GB Sala-Newby, SJ George

Research output: Contribution to journalArticle (Academic Journal)peer-review

40 Citations (Scopus)

Abstract

OBJECTIVE: Vascular smooth muscle cell (VSMC) apoptosis contributes to atherosclerotic plaque instability and myocardial infarction. Consequently, reducing VSMC apoptosis may be beneficial for reducing plaque instability and acute coronary events. We previously demonstrated that N-Cadherin, a cell-cell adhesion molecule, reduces VSMC apoptosis in vitro. In this study, we examined whether a soluble form of N-cadherin (SNC) affected VSMC apoptosis and plaque stability. METHODS AND RESULTS: SNC significantly inhibited VSMC apoptosis in vitro by approximately 50% via activation of fibroblast growth factor receptor, phosphoinositide-3 kinase, and Akt signaling. SNC also significantly reduced macrophage and foam cell-macrophage apoptosis in vitro by >50%, without affecting monocyte invasion or macrophage proliferation. Elevation of plasma levels of SNC in male apolipoprotein E-deficient mice with existing atherosclerosis via adenoviral delivery significantly reduced VSMC and macrophage apoptosis in brachiocephalic artery plaques by approximately 60%. Additionally, SNC promoted plaques of a more stable phenotype by elevating VSMC:macrophage ratio and presence of VSMC-rich fibrous cap, as well as attenuating macrophage number and incidence of buried fibrous caps (a surrogate plaque rupture marker). CONCLUSIONS: In summary, this study demonstrates that SNC suppressed plaque instability by attenuation of apoptosis, suggesting that SNC may have a therapeutic potential for retarding plaque instability.
Translated title of the contributionSoluble N-Cadherin Overexpression Reduces Features of Atherosclerotic Plaque Instability
Original languageEnglish
Pages (from-to)195 - 201
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume29
Issue number2
Early online date13 Nov 2008
DOIs
Publication statusPublished - Feb 2009

Bibliographical note

Publisher: American Heart Association

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