title: Nonenzymatic glycation interferes with fibronectin-integrin interactions in vascular smooth muscle cells.
abstract: We aimed to investigate whether advanced nonenzymatic glycation of the ECM protein, fibronectin, impacts its normal integrin-mediated interaction with arteriolar VSMC.
  
  
  
  AFM was performed on cultured VSMC from rat cremaster arterioles to study native and glycated fibronectin (FN and gFN) interactions with cellular integrins. AFM probes were functionalized with FN or gFN or with native or glycated albumin (gAlb) as controls.
  
  
  
  VSMC showed increased adhesion probability to gFN (72.9±3.5%) compared with native FN (63.0±1.6%). VSMC similarly showed increased probability of adhesion (63.8±1.7%) to gAlb compared with native Alb (40.1±4.7%). Adhesion of native FN to VSMC was α5 and β1 integrin dependent whereas adhesion of gFN to VSMC was integrin independent. The RAGE-selective inhibitor, FPS-ZM1, blocked gFN (and gAlb) adhesion, suggesting that adhesion of glycated proteins was RAGE dependent. Interaction of FN with VSMC was not altered by soluble gFN while soluble native FN did not inhibit adhesion of gFN to VSMC. In contrast, gAlb inhibited adhesion of gFN to VSMC in a concentration-dependent manner.
  
  
  
  Glycation of FN shifts the nature of cellular adhesion from integrin- to RAGE-dependent mechanisms.
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.|Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA.
authors.forename: Srijita
authors.initials: S
authors.lastname: Dhar
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.|Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Meininger
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.|Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA.
authors.forename: Michael A
authors.identifier: 0000-0002-4455-2072
authors.initials: MA
authors.lastname: Hill
mesh_terms: D000818:Animals; D001160:Arterioles / Q000166:cytology*; D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism*; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D016023:Integrins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D012709:Serum Albumin / Q000378:metabolism; D000093423:Glycated Serum Albumin; D000093844:Glycated Proteins
chemical_list: D005353:Fibronectins; D017127:Glycation End Products, Advanced; D016023:Integrins; D000067759:Receptor for Advanced Glycation End Products; D012709:Serum Albumin; D000093423:Glycated Serum Albumin; C000593874:Ager protein, rat; C045099:glycated fibronectin; D000093844:Glycated Proteins
keywords: adhesion; advanced glycation end products; atomic force microscopy; extracellular matrix proteins; integrins; receptor for advanced glycation end products; resistance arteries