title: Systemic inflammation as a predictor of clinical outcomes after lower extremity angioplasty/stenting.
abstract: The activation state of the systemic inflammatory milieu has been proposed as a critical regulator of vascular repair after injury. We evaluated the early inflammatory response after endovascular intervention for symptomatic peripheral arterial disease to determine its association with clinical success or failure.
  
  
  
  Blood samples were obtained from 14 patients undergoing lower extremity angioplasty/stenting and analyzed using high-throughput gene arrays, multiplex serum protein analyses, and flow cytometry.
  
  
  
  Time-dependent plasma protein and monocyte phenotype analyses demonstrated endovascular revascularization had a modest influence on the overall activation state of the systemic inflammatory system, with baseline variability exceeding the perturbations induced by the intervention. In contrast, specific time-dependent changes in the monocyte genome are evident in the initial 28 days, predominately in those genes associated with leukocyte extravasation. Investigating the relationship between inflammation and the 1-year success or failure of the intervention showed no single plasma protein was correlated with outcome, but a more comprehensive cluster analysis revealed a clear pattern of protein expression that was closely related to the clinical phenotype. Corresponding examination of the monocyte genome identified a gene subset at 1 day postprocedure that was predictive of clinical outcome, with most of these genes active in cell-cycle signaling.
  
  
  
  Although the global influence of angioplasty/stenting on systemic inflammation was modest, circulating cytokine and monocyte genome analyses support a pattern of early inflammation that is associated with ultimate intervention success vs failure. Molecular profiles incorporating genes involved in monocyte cell-cycle progression and homing, or proinflammatory cytokines, or both, offer the most promise for the development of class prediction tools for clinical application.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Fla.
authors.forename: Kenneth
authors.initials: K
authors.lastname: DeSart
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Fla.
authors.forename: Kerri
authors.initials: K
authors.lastname: O'Malley
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Fla.
authors.forename: Bradley
authors.initials: B
authors.lastname: Schmit
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Fla.
authors.forename: Maria-Cecilia
authors.initials: MC
authors.lastname: Lopez
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Fla.
authors.forename: Lyle
authors.initials: L
authors.lastname: Moldawer
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Fla.
authors.forename: Henry
authors.initials: H
authors.lastname: Baker
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Fla; Malcom Randall VA Medical Center, Gainesville, Fla.
authors.forename: Scott
authors.initials: S
authors.lastname: Berceli
authors.affiliation: Division of Vascular and Endovascular Surgery, University of South Florida Morsani College of Medicine, Tampa, Fla; James A. Haley VA Medical Center, Tampa, Fla. Electronic address: pnelson1@health.usf.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Nelson
mesh_terms: D000368:Aged; D000800:Angioplasty, Balloon / Q000009:adverse effects* / Q000295:instrumentation*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D058729:Peripheral Arterial Disease / Q000000981:diagnostic imaging / Q000628:therapy*; D010641:Phenotype; D012307:Risk Factors; D015607:Stents; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D018836:Inflammation Mediators