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Open Access Research article

Gene expression differences during the heterogeneous progression of peripheral atherosclerosis in familial hypercholesterolemic swine

Martin Bahls12*, Christopher A Bidwell3, Juan Hu4, Armando Tellez5, Greg L Kaluza5, Juan F Granada5, Christian G Krueger6, Jess D Reed6, M Harold Laughlin7, William G Van Alstine8 and Sean C Newcomer19

Author Affiliations

1 Department of Health and Kinesiology, Purdue University, West Lafayette, IN, USA

2 Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere Medizin B, Ferdinand-Sauerbruch-Str., Greifswald, Germany

3 Department of Animal Science, Purdue University, West Lafayette, IN, USA

4 Department of Statistics, Purdue University, West Lafayette, IN, USA

5 Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, New York, USA

6 Department of Animal Science, University of Wisconsin, Madison, WI, USA

7 Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA

8 Department of Veterinary Pathobiology, Purdue University, West Lafayette, IN, USA

9 California State University San Marcos, San Marcos, CA, USA

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BMC Genomics 2013, 14:443  doi:10.1186/1471-2164-14-443

Published: 3 July 2013

Abstract

Background

The heterogeneous progression of atherosclerotic disease in the peripheral arteries is currently not well understood. In humans, artery specific disease progression is partly attributed to the local hemodynamic environments. However, despite similar hemodynamic environments, porcine brachial arteries are protected while femoral arteries are highly susceptible to advanced lesion formation. The aim of this investigation was to determine whether artery specific gene expression patterns contribute to the uneven distribution of peripheral arterial disease (PAD) in Rapacz Familial-Hypercholesterolemic (FHC) swine.

Results

Histological results confirmed rapid atherosclerotic disease progression in femoral but not brachial arteries. A total of 18,922 probe sets had sufficient signal abundance. A main effect for age and artery was observed for 1784 and 1256 probe sets, respectively. A significant age x artery interaction was found for 184 probe sets. Furthermore, comparison between arteries found a decrease from 714 to 370 differentially expressed transcripts from nine months to two years of age. Gene ontology analysis of the 56 genes with a main effect for artery and an age x artery interaction identified vascular smooth muscle contraction as enhanced biological signaling pathway.

Conclusion

This is the first investigation to report that the total number of differential genes decreases with diverging atherosclerotic disease pattern between porcine brachial and femoral arteries.

Keywords:
Peripheral arterial disease; Atherosclerosis; Vascular biology; Peripheral vasculature; Gene expression