title: Genomic and proteomic determinants of lower extremity revascularization failure: rationale and study design.
abstract: This translational research program applies a working model of advanced functional genomics/proteomics and bioinformatics to human peripheral arterial occlusive disease (PAOD). It is a multidisciplinary collaborative effort of clinicians, scientists, and statisticians with an advisory panel consisting of experts in inflammation biology, vascular biology, molecular genetics, bioinformatics, clinical trial design, and epidemiology. The proposed human initiative is designed to study 300 symptomatic patients with PAOD undergoing medical management with or without vascular intervention by lower extremity angioplasty/stenting or vein graft bypass. The study aims to test the hypothesis that the systemic inflammatory response after vascular intervention influences the local milieu responsible for vascular repair and adaptation. The expectation is that this response is not uniform in all patients but, rather, is modulated by either preoperative genetic predisposition or postprocedure differential regulation of the innate immune response to injury that promotes a maladaptive phenotype leading to intervention failure. Therefore, some of these differences may be present and detectable before intervention and amenable to class prediction and prospective treatment strategies, whereas others may be detectable in the early postprocedural period, before the onset of clinical failure, permitting interventions to prevent an adverse outcome. The combination of genomic/proteomic data together with functional and quality-of-life outcome measures to define a critical model for class prediction and analysis should lead to new knowledge about failure mechanisms of vascular intervention and new strategies to improve existing approaches to lower extremity revascularization.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA. peter.nelson@surgery.ufl.edu
authors.forename: Peter R
authors.initials: PR
authors.lastname: Nelson
authors.forename: Kerri A
authors.initials: KA
authors.lastname: O'Malley
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Feezor
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: James M
authors.initials: JM
authors.lastname: Seeger
mesh_terms: D000328:Adult; D017130:Angioplasty / Q000009:adverse effects / Q000295:instrumentation; D001157:Arterial Occlusive Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D002986:Clinical Trials as Topic; D016000:Cluster Analysis; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods*; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008137:Longitudinal Studies; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016491:Peripheral Vascular Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D025341:Principal Component Analysis; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods*; D011788:Quality of Life; D020127:Recovery of Function; D012107:Research Design; D015607:Stents; D017211:Treatment Failure; D014656:Vascular Surgical Procedures / Q000009:adverse effects*; D014680:Veins / Q000637:transplantation
chemical_list: D047908:Intracellular Signaling Peptides and Proteins