Summary of Study ST000185

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000158. The data can be accessed directly via it's Project DOI: 10.21228/M8T01Q This work is supported by NIH grant, U2C- DK119886.

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Study IDST000185
Study TitleFetal Lambs vascular graft Normal v Shunt LECs
Study TypeGlycolysis/TCA/Nucleotide analysis (tissue/cells)
Study SummaryWe recently reported superior right ventricle (RV) performance in response to acute afterload challenge in lambs with a model of congenital heart disease with chronic left-to-right cardiac shunts. Compared with control animals, shunt lambs demonstrated increased contractility because of an enhanced Anrep effect (the slow increase in contractility following myocyte stretch). This advantageous physiological response may reflect preservation of a fetal phenotype, since the RV of shunt lambs remains exposed to increased pressure postnatally. Nitric oxide (NO) production by NO synthase (NOS) is activated by myocyte stretch and is a necessary intermediary of the Anrep response. The purpose of this study was to test the hypothesis that NO signaling is increased in the RV of fetal lambs compared with controls and shunt lambs have persistence of this fetal pattern. An 8-mm graft was placed between the pulmonary artery and aorta in fetal lambs (shunt). NOS isoform expression, activity, and association with activating cofactors were determined in fetal tissue obtained during late-gestation and in 4-wk-old juvenile shunt and control lambs. We demonstrated increased RNA and protein expression of NOS isoforms and increased total NOS activity in the RV of both shunt and fetal lambs compared with control. We also found increased NOS activation and association with cofactors in shunt and fetal RV compared with control. These data demonstrate preserved fetal NOS phenotype and NO signaling in shunt RV, which may partially explain the mechanism underlying the adaptive response to increased afterload seen in the RV of shunt lambs. Research is published, core data not used but project description is relevant: http://ajpheart.physiology.org/content/309/1/H157.long
Institute
University of Michigan
DepartmentBiomedical Research Core Facilities
LaboratoryMetabolomics core
Last NameKachman
First NameMaureen
Address6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Email mkachman@umich.edu
Submit Date2015-06-07
Num Groups2
Total Subjects6
Raw Data AvailableYes
Raw Data File Type(s)d
Uploaded File Size512 M
Analysis Type DetailGC-MS/LC-MS
Release Date2015-12-28
Release Version1
Maureen Kachman Maureen Kachman
https://dx.doi.org/10.21228/M8T01Q
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000158
Project DOI:doi: 10.21228/M8T01Q
Project Title:LEC metabolomics
Project Summary:Comparison of metabolomic profile in LECs derived from normal and shunt animals
Institute:University of California, San Francisco
Department:Pediatrics
Laboratory:Fineman Lab
Last Name:Fineman
First Name:Jeffrey
Address:San Francisco, CA
Email:jeff.fineman@ucsf.edu
Phone:415-502-6390
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