title: Soluble N-cadherin overexpression reduces features of atherosclerotic plaque instability.
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.
  
  
  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.
authors.affiliation: Bristol Heart Institute, Bristol Royal Infirmary, UK.
authors.forename: Cressida A
authors.initials: CA
authors.lastname: Lyon
authors.forename: Jason L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Helen
authors.initials: H
authors.lastname: Williams
authors.forename: Graciela B
authors.initials: GB
authors.lastname: Sala-Newby
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: George
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016122:Brachiocephalic Trunk / Q000378:metabolism / Q000473:pathology*; D016466:CHO Cells; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002448:Cell Adhesion; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000096:biosynthesis; D015398:Signal Transduction; D013997:Time Factors; D014161:Transduction, Genetic; D015854:Up-Regulation
chemical_list: D001057:Apolipoproteins E; D015820:Cadherins; D010446:Peptide Fragments