Soluble N-Cadherin Overexpression Reduces Features of Atherosclerotic Plaque Instability

Lyon, Cressida A.; Johnson, Jason L.; Williams, Helen; Sala-Newby, Graciela B.; George, Sarah J.

doi:10.1161/atvbaha.108.178087

Cited by 51Atherosclerosis and Cardiovascular DiseasesCerebrovascular and Carotid Artery DiseasesCholesterol and Lipid Metabolism

Soluble N-Cadherin Overexpression Reduces Features of Atherosclerotic Plaque Instability

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Lyon, Cressida A., Johnson, Jason L., Williams, Helen, Sala-Newby, Graciela B., George, Sarah J.·2009·Arteriosclerosis, Thrombosis, and Vascular Biology

DOI 10.1161/atvbaha.108.178087PMC PMC2853707

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Abstract

Objectives— 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 ≈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 ≈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.

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Cell to cell contact via N-cadherin promotes VSMC survival.
“Similarly, cell to cell contact via N-cadherin promotes survival 181 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [181]

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Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis
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Authors: Lyon, C. A., Johnson, J. L., Williams, H., Sala-Newby, G. B., & George, S. J.
Affiliations: Bristol Royal Infirmary (GB)
From the Bristol Heart Institute, Bristol Royal Infirmary, UK.
ORCID: Lyon, Cressida A.
Johnson, Jason L.
Williams, Helen
George, Sarah J.
Venue: Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2009-02
Volume: 29
Issue: 2
Pages: 195-201
ISSN: 1079-5642 (ISSN-L)
1524-4636
DOI: 10.1161/atvbaha.108.178087
PMC: PMC2853707
OpenAlex: W2151483213
Cited by: 51
References: 48
Citations by year: 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 5 · 2017: 5 · 2016: 1 · 2015: 3 · 2014: 8 · 2013: 5 · 2012: 1
FWCI: 1.67
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Bristol Research (University of Bristol) (submittedVersion)
Funders: British Heart Foundation (FS/03/080/15921, PG/07/081/23619)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords: atherosclerotic plaque instability, vascular smooth muscle cell apoptosis, macrophage apoptosis, foam cells, fibroblast growth factor receptor, phosphatidylinositol 3-kinase/Akt signaling, ApoE-deficient mice, fibrous cap, plaque rupture, cell-cell adhesion molecules
MeSH terms: Adenoviridae, Animals, Apolipoproteins E, Cell Adhesion, Cricetulus, Disease Models, Animal, Foam Cells, Genetic Vectors, Cricetinae, Humans, Male, Mice, Inbred C57BL, Monocytes, Muscle, Smooth, Vascular, Peptide Fragments, Time Factors, Transduction, Genetic, Genetic Therapy, Signal Transduction, Cadherins, Up-Regulation, Brachiocephalic Trunk, CHO Cells, Apoptosis, Mice, Knockout, Myocytes, Smooth Muscle, Atherosclerosis, Mice

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Soluble N-Cadherin Overexpression Reduces Features of Atherosclerotic Plaque Instability

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