Document Detail

Genomic and proteomic determinants of lower extremity revascularization failure: rationale and study design.
MedLine Citation:
PMID:  17544028     Owner:  NLM     Status:  MEDLINE    
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.
Peter R Nelson; Kerri A O'Malley; Robert J Feezor; Lyle L Moldawer; James M Seeger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of vascular surgery     Volume:  45 Suppl A     ISSN:  0741-5214     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-08-06     Completed Date:  2007-08-24     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  A82-91     Citation Subset:  IM    
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MeSH Terms
Angioplasty / adverse effects,  instrumentation
Arterial Occlusive Diseases / drug therapy,  genetics,  metabolism,  physiopathology,  surgery,  therapy*
Clinical Trials as Topic*
Cluster Analysis
Computational Biology*
Gene Expression Profiling
Genomics / methods*
Inflammation / etiology*,  genetics,  metabolism,  physiopathology
Intracellular Signaling Peptides and Proteins / genetics,  metabolism
Longitudinal Studies
Lower Extremity / blood supply*
Oligonucleotide Array Sequence Analysis
Peripheral Vascular Diseases / drug therapy,  genetics,  metabolism,  physiopathology,  surgery,  therapy*
Principal Component Analysis
Prospective Studies
Proteomics / methods*
Quality of Life
Recovery of Function
Research Design
Treatment Failure
Vascular Surgical Procedures / adverse effects*
Veins / transplantation
Grant Support
1K23HL084009-01/HL/NHLBI NIH HHS; 2T32GM08721/GM/NIGMS NIH HHS; K23 HL084090/HL/NHLBI NIH HHS; K23 HL084090-01/HL/NHLBI NIH HHS; L30 HL086135/HL/NHLBI NIH HHS; L30 HL086135-01/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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