title: Gene Expression in Experimental Aortic Coarctation and Repair: Candidate Genes for Therapeutic Intervention?
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.
authors.affiliation: Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, United States of America; Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America; Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America; Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: John F
authors.initials: JF
authors.lastname: LaDisa
authors.affiliation: Department of Mathematics, Statistics, and Computer Science, Marquette University, Milwaukee, Wisconsin, United States of America.
authors.forename: Serdar
authors.initials: S
authors.lastname: Bozdag
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Olson
authors.affiliation: Departments of Pediatrics and Obstetrics and Gynecology, Medical College of Wisconsin and the Developmental Vascular Biology Program, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Ramani
authors.initials: R
authors.lastname: Ramchandran
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Judy R
authors.initials: JR
authors.lastname: Kersten
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin, United States of America.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Eddinger
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology*; D001017:Aortic Coarctation / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D058977:Molecular Sequence Annotation; D011817:Rabbits