Journal article
Role of genetics in peripheral arterial disease outcomes; significance of limb-salvage quantitative locus-1 genes
Experimental biology and medicine (Maywood, N.J.), Vol.243(2), pp.190-197
01/01/2018
DOI: 10.1177/1535370217743460
PMCID: PMC5788144
PMID: 29199462
Abstract
Peripheral artery disease is a major health care problem with significant morbidity and mortality. Humans with peripheral artery disease exhibit two major and differential clinical manifestations - intermittent claudication and critical limb ischemia. Individuals with intermittent claudication or critical limb ischemia have overlapping risk factors and objective measures of blood flow. Hence, we hypothesized that variation in genetic make-up may be an important determinant in the severity of peripheral artery disease. Previous studies have identified polymorphism in genes, contributing to extent of atherosclerosis but much less is known about polymorphisms associated with genes that can influence peripheral artery disease severity. This review outlines some of the progress made up-to-date to unravel the molecular mechanisms underlining differential peripheral artery disease severity. By exploring the recovery phenotype of different mouse strains following experimental peripheral artery disease, our group identified the limb salvage-associated quantitative trait locus 1 on mouse chromosome 7 as the first genetic modifier of perfusion recovery and tissue necrosis phenotypes. Furthermore, a number of genes within LSq-1, such as ADAM12, IL-21Ra, and BAG3 were identified as genetic modifiers of peripheral artery disease severity that function through preservation of endothelial and skeletal muscle cells during ischemia. Taken together, these studies suggest manipulation of limb salvage-associated quantitative trait locus 1 genes show great promise as therapeutic targets in the management of peripheral artery disease.
Details
- Title: Subtitle
- Role of genetics in peripheral arterial disease outcomes; significance of limb-salvage quantitative locus-1 genes
- Creators
- Emmanuel Okeke - University of Tennessee Health Science CenterAyotunde O. Dokun - University of Tennessee Health Science Center
- Resource Type
- Journal article
- Publication Details
- Experimental biology and medicine (Maywood, N.J.), Vol.243(2), pp.190-197
- Publisher
- Sage
- DOI
- 10.1177/1535370217743460
- PMID
- 29199462
- PMCID
- PMC5788144
- ISSN
- 1535-3702
- eISSN
- 1535-3699
- Number of pages
- 8
- Grant note
- 3 R01 HL101200-01S1; R01HL130399 / NIH NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Harold Amos Medical Faculty Development Program award R01HL101200 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Robert Wood Johnson Foundation; Robert Wood Johnson Foundation (RWJF)
- Language
- English
- Date published
- 01/01/2018
- Academic Unit
- Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984297612802771
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