RGD Reference Report - Placental growth factor regulates cardiac inflammation through the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-alpha-converting enzyme axis: crucial role for adaptive cardiac remodeling during cardiac pressure overload. - Rat Genome Database

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Placental growth factor regulates cardiac inflammation through the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-alpha-converting enzyme axis: crucial role for adaptive cardiac remodeling during cardiac pressure overload.

Authors: Carnevale, D  Cifelli, G  Mascio, G  Madonna, M  Sbroggio, M  Perrino, C  Persico, MG  Frati, G  Lembo, G 
Citation: Carnevale D, etal., Circulation. 2011 Sep 20;124(12):1337-50. Epub 2011 Sep 6.
RGD ID: 6483574
Pubmed: PMID:21900081   (View Abstract at PubMed)
DOI: DOI:10.1161/CIRCULATIONAHA.111.050500   (Journal Full-text)

BACKGROUND: Heart failure is one of the leading causes of mortality and is primarily the final stage of several overload cardiomyopathies, preceded by an early adaptive hypertrophic response and characterized by coordinated cardiomyocyte growth, angiogenesis, and inflammation. Therefore, growth factors and cytokines have to be critically regulated during cardiac response to transverse aortic constriction. Interestingly, the dual properties of placental growth factor as an angiogenic factor and cytokine make it a candidate to participate in cardiac remodeling in response to hemodynamic overload. METHODS AND RESULTS: After transverse aortic constriction, placental growth factor knockout mice displayed a dysregulation of cardiac remodeling, negatively affecting muscle growth. Molecular insights underscored that this effect was ascribable mainly to a failure in the establishment of adequate inflammatory response owing to an impaired activity of tumor necrosis factor-alpha-converting enzyme. Interestingly, after transverse aortic constriction, placental growth factor knockout mice had strongly increased levels of tissue inhibitor of metalloproteinases-3, the main natural TACE inhibitor, thus indicating an unbalance of the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-alpha-converting enzyme axis. Strikingly, when we used an in vivo RNA interference approach to reduce tissue inhibitor of metalloproteinases-3 levels in placental growth factor knockout mice during transverse aortic constriction, we obtained a complete phenotype rescue of early dilated cardiomyopathy. CONCLUSIONS: Our results demonstrate that placental growth factor finely tunes a balanced regulation of the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-alpha-converting enzyme axis and the consequent TNF-alpha activation in response to transverse aortic constriction, thus allowing the establishment of an inflammatory response necessary for adaptive cardiac remodeling.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PGFHumandilated cardiomyopathy  ISOPgf (Mus musculus) RGD 
PgfRatdilated cardiomyopathy  ISOPgf (Mus musculus) RGD 
PgfMousedilated cardiomyopathy  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pgf  (placental growth factor)

Genes (Mus musculus)
Pgf  (placental growth factor)

Genes (Homo sapiens)
PGF  (placental growth factor)


Additional Information