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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2009-11-25
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pubmed:abstractText |
The heart adapts to an increased workload through the activation of a hypertrophic response within the cardiac ventricles. This response is characterized by both an increase in the size of the individual cardiomyocytes and an induction of a panel of genes normally expressed in the embryonic and neonatal ventricle, such as atrial natriuretic peptide (ANP). ANP and brain natriuretic peptide (BNP) exert their biological actions through activation of the natriuretic peptide receptor-1 (Npr1). The current study examined mice lacking Npr1 (Npr1(-/-)) activity and investigated the effects of the absence of Npr1 signaling during cardiac development on embryo viability, cardiac structure and gene and protein expression. Npr1(-/-)embryos were collected at embryonic day (ED) 12.5, 15.5 and neonatal day 1 (ND 1). Npr1(-/-)embryos occurred at the expected Mendelian frequency at ED 12.5, but knockout numbers were significantly decreased at ED 15.5 and ND 1. There was no indication of cardiac structural abnormalities in surviving embryos. However, Npr1(-/-)embryos exhibited cardiac enlargement (without fibrosis) from ED 15.5 as well as significantly increased ANP mRNA and protein expression compared to wild-type (WT) mice, but no concomitant increase in expression of the hypertrophy-related transcription factors, Mef2A, Mef2C, GATA-4, GATA-6 or serum response factor (SRF). However, there was a significant decrease in Connexin-43 (Cx43) gene and protein expression at mid-gestation in Npr1(-/-)embryos. Our findings suggest that the mechanism by which natriuretic peptide signaling influences cardiac development in Npr1(-/-) mice is distinct from that seen during the development of pathological cardiac hypertrophy and fibrosis. The decreased viability of Npr1(-/-)embryos may result from a combination of cardiomegaly and dysregulated Cx43 protein affecting cardiac contractility.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/R01 HL049277-14,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL049277-15,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL049277-16,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL049277-17,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL049277-18,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL062845-01,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL062845-02,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL062845-03,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL062845-04,
http://linkedlifedata.com/resource/pubmed/grant/R37 HL042630-16,
http://linkedlifedata.com/resource/pubmed/grant/R37 HL042630-17,
http://linkedlifedata.com/resource/pubmed/grant/R37 HL042630-18,
http://linkedlifedata.com/resource/pubmed/grant/R37 HL042630-19
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0006-3002
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
1792
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1175-84
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pubmed:dateRevised |
2011-3-3
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pubmed:meshHeading |
pubmed-meshheading:19782130-Animals,
pubmed-meshheading:19782130-Atrial Natriuretic Factor,
pubmed-meshheading:19782130-Blood Pressure,
pubmed-meshheading:19782130-Blotting, Western,
pubmed-meshheading:19782130-Cardiomegaly,
pubmed-meshheading:19782130-Connexin 43,
pubmed-meshheading:19782130-Embryo, Mammalian,
pubmed-meshheading:19782130-Female,
pubmed-meshheading:19782130-Gene Expression Regulation, Developmental,
pubmed-meshheading:19782130-Heart,
pubmed-meshheading:19782130-Immunoenzyme Techniques,
pubmed-meshheading:19782130-Male,
pubmed-meshheading:19782130-Mice,
pubmed-meshheading:19782130-Mice, Knockout,
pubmed-meshheading:19782130-Natriuretic Peptide, Brain,
pubmed-meshheading:19782130-RNA, Messenger,
pubmed-meshheading:19782130-Receptors, Atrial Natriuretic Factor,
pubmed-meshheading:19782130-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19782130-Survival Rate,
pubmed-meshheading:19782130-Transcription Factors
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pubmed:year |
2009
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pubmed:articleTitle |
Influence of natriuretic peptide receptor-1 on survival and cardiac hypertrophy during development.
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pubmed:affiliation |
Department of Medicine, University of Otago-Christchurch, P.O. Box 4345, Christchurch, New Zealand. nicola.scott@otago.ac.nz
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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