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Gene Expression in Experimental Aortic Coarctation and Repair: Candidate Genes for Therapeutic Intervention? PLoS One 2015;10(7):e0133356

Date

07/25/2015

Pubmed ID

26207811

Pubmed Central ID

PMC4514739

DOI

10.1371/journal.pone.0133356

Abstract

Coarctation of the aorta (CoA) is a constriction of the proximal descending thoracic aorta and is one of the most common congenital cardiovascular defects. Treatments for CoA improve life expectancy, but morbidity persists, particularly due to the development of chronic hypertension (HTN). Identifying the mechanisms of morbidity is difficult in humans due to confounding variables such as age at repair, follow-up duration, coarctation severity and concurrent anomalies. We previously developed an experimental model that replicates aortic pathology in humans with CoA without these confounding variables, and mimics correction at various times using dissolvable suture. Here we present the most comprehensive description of differentially expressed genes (DEGs) to date from the pathology of CoA, which were obtained using this model. Aortic samples (n=4/group) from the ascending aorta that experiences elevated blood pressure (BP) from induction of CoA, and restoration of normal BP after its correction, were analyzed by gene expression microarray, and enriched genes were converted to human orthologues. 51 DEGs with >6 fold-change (FC) were used to determine enriched Gene Ontology terms, altered pathways, and association with National Library of Medicine Medical Subject Headers (MeSH) IDs for HTN, cardiovascular disease (CVD) and CoA. The results generated 18 pathways, 4 of which (cell cycle, immune system, hemostasis and metabolism) were shared with MeSH ID's for HTN and CVD, and individual genes were associated with the CoA MeSH ID. A thorough literature search further uncovered association with contractile, cytoskeletal and regulatory proteins related to excitation-contraction coupling and metabolism that may explain the structural and functional changes observed in our experimental model, and ultimately help to unravel the mechanisms responsible for persistent morbidity after treatment for CoA.

Author List

LaDisa JF Jr, Bozdag S, Olson J, Ramchandran R, Kersten JR, Eddinger TJ

Authors

Serdar Bozdag BS,PhD Assistant Professor, Director of Bioinformatics Lab in the Dept. of Mathematics, Statistics and Computer Science department at Marquette University
Thomas Eddinger PhD Bioological Sciences in the Biology department at Marquette University
John LaDisa PhD Assistant Professor in the Biomedical Engineering department at Marquette University
Jessica Olson PhD Director, Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Aorta
Aortic Coarctation
Disease Models, Animal
Gene Expression
Gene Expression Profiling
Humans
Male
Molecular Sequence Annotation
Rabbits