title: Correlation between gene expression and morphological alterations in baboon carotid after balloon dilatation injury.
abstract: Treatment for fibroproliferative restenosis after angioplasty and endovascular surgery is an unmet medical need. Rational therapy and drug design still lack the very basic knowledge about the underlying biological processes leading to pathological changes in the vessel wall. We have developed a primate model for vascular response to denudation-overstretch injury of baboon carotid artery. With this model, we have investigated the time course of vascular expression of 41,000 human cDNA clones and correlated these changes with carotid histology and function. Analysis revealed 20,788 differentially regulated cDNA clones. After high stringency data selection, the most prominently regulated 1629 cDNA clones representing 1510 genes of known function were clustered. Genes corresponding to functional and anatomical alterations in the injured carotid wall were further aligned into functional groups according to Gene Ontology classification. The observed expression patterns faithfully reflected the functional and anatomical alterations observed in the vascular wall in response to injury. The analysis presents a tentative model for genomic response to balloon catheter injury and a road map to identify time-related genomic alterations in human vascular specimens.
authors.affiliation: Rational Drug Design Program, Biomedicum and Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Einari
authors.initials: E
authors.lastname: Aavik
authors.forename: Ajit
authors.initials: A
authors.lastname: Mahapatra
authors.forename: Jennifer
authors.initials: J
authors.lastname: Boldrick
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Christopher
authors.initials: C
authors.lastname: Barry
authors.forename: Daniel
authors.initials: D
authors.lastname: Dutoit
authors.forename: Minnie
authors.initials: M
authors.lastname: Sarwal
authors.forename: Pekka
authors.initials: P
authors.lastname: Häyry
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000737:chemistry / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D002404:Catheterization / Q000009:adverse effects* / Q000379:methods; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D005796:Genes / Q000502:physiology; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009693:Nucleic Acid Hybridization / Q000379:methods; D048549:Papio ursinus / Q000235:genetics*; D011506:Proteins / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D011506:Proteins