title: Early changes of gene expression profiles in the rat model of arterial injury.
abstract: OBJECTIVE
  Restenosis caused by intimal hyperplasia (IH) remains a significant drawback for vascular interventions. It is crucial to understand the molecular mechanisms that control activation of smooth muscle cells (SMCs) after the injury in order to develop strategies to prevent IH. The purpose of the present study was to investigate the early alterations in arterial-wall gene expression after balloon injury in the rat carotid artery with focus on the induction of an inflammatory response.
  
  
  METHODS
  Twenty-four male Sprague-Dawley rats were subjected to injury of the left common carotid artery by using a 2-F Fogarty catheter. The arteries were harvested 5, 10, and 20 hours after injury. Uninjured arteries from an additional eight rats were used as controls. RNA was isolated and used for genome-wide microarray expression analysis, followed by validation of selected genes with quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed on the cross-sectioned vessels.
  
  
  RESULTS
  Analysis of gene expression by microarrays showed that the most differentially expressed genes were primarily associated with inflammation, cell proliferation, migration, and adhesion. As confirmed by qRT-PCR, microarray data showed a significant (P < .005) upregulation of cytokines and chemokines (IL-6, CCL2, CXCL1, AIMP1, and CD44) just 5 hours after injury. Immunohistochemistry demonstrated that CCL2 and the adhesion receptor CD44 were expressed by SMCs in the early response to injury and in the absence of leukocyte infiltration.
  
  
  CONCLUSIONS
  Arterial injury is followed by an early induction of inflammatory genes in the vessel wall that appears to be confined to SMCs.
authors: Institute of Molecular Biology and Genetics, Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, Russia; Ariadne Genomics, Rockville, Maryland.
authors: Anton
authors: A
authors: Fedorov
authors: Institute of Molecular Biology and Genetics, Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, Russia; Women's and Children's Health, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors: Anna
authors: A
authors: Kostareva
authors: Physiology and Pharmacology, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors: Johan
authors: J
authors: Raud
authors: Center for Molecular Medicine and Division of Vascular Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors: Joy
authors: J
authors: Roy
authors: Center for Molecular Medicine and Division of Vascular Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors: Ulf
authors: U
authors: Hedin
authors: Center for Molecular Medicine and Division of Vascular Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Electronic address: anton.razuvaev@ki.se.
authors: Anton
authors: A
authors: Razuvaev
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000276:immunology* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000276:immunology* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators