Document Detail


Placental growth factor regulates cardiac adaptation and hypertrophy through a paracrine mechanism.
MedLine Citation:
PMID:  21636802     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Paracrine growth factor-mediated crosstalk between cardiac myocytes and nonmyocytes in the heart is critical for programming adaptive cardiac hypertrophy in which myocyte size, capillary density, and the extracellular matrix function coordinately.
OBJECTIVE: To examine the role that placental growth factor (PGF) plays in the heart as a paracrine regulator of cardiac adaptation to stress stimulation.
METHODS AND RESULTS: PGF is induced in the heart after pressure-overload stimulation, where it is expressed in both myocytes and nonmyocytes. We generated cardiac-specific and adult inducible PGF-overexpressing transgenic mice and analyzed Pgf(-/-) mice to examine the role that this factor plays in cardiac disease and paracrine signaling. Although PGF transgenic mice did not have a baseline phenotype or a change in capillary density, they did exhibit a greater cardiac hypertrophic response, a greater increase in capillary density, and increased fibroblast content in the heart in response to pressure-overload stimulation. PGF transgenic mice showed a more adaptive type of cardiac growth that was protective against signs of failure with pressure overload and neuroendocrine stimulation. Antithetically, Pgf(-/-) mice rapidly died of heart failure within 1 week of pressure overload, they showed an inability to upregulate angiogenesis, and they showed significantly less fibroblast activity in the heart. Mechanistically, we show that PGF does not have a direct effect on cardiomyocytes but works through endothelial cells and fibroblasts by inducing capillary growth and fibroblast proliferation, which secondarily support greater cardiac hypertrophy through intermediate paracrine growth factors such as interleukin-6.
CONCLUSIONS: PGF is a secreted factor that supports hypertrophy and cardiac function during pressure overload by affecting endothelial cells and fibroblasts that in turn stimulate and support the myocytes through additional paracrine factors.
Authors:
Federica Accornero; Jop H van Berlo; Matthew J Benard; John N Lorenz; Peter Carmeliet; Jeffery D Molkentin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-06-02
Journal Detail:
Title:  Circulation research     Volume:  109     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-22     Completed Date:  2011-09-22     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  272-80     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological / physiology
Animals
Blood Pressure / physiology
Cardiomegaly / metabolism*,  physiopathology*
Coronary Circulation / physiology
Endothelial Cells / physiology
Extracellular Matrix / physiology
Fibroblasts / physiology
Mice
Mice, Transgenic
Myocytes, Cardiac / physiology*
Neovascularization, Pathologic / metabolism,  physiopathology
Neovascularization, Physiologic / physiology
Paracrine Communication / physiology*
Pregnancy Proteins / genetics,  metabolism*
Stress, Physiological / physiology
Grant Support
ID/Acronym/Agency:
R01 HL062927/HL/NHLBI NIH HHS; R01 HL062927-13/HL/NHLBI NIH HHS; R01 HL105924/HL/NHLBI NIH HHS; R01 HL105924-02/HL/NHLBI NIH HHS; R37 HL060562/HL/NHLBI NIH HHS; R37 HL060562-14/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Pregnancy Proteins; 144589-93-5/placenta growth factor
Comments/Corrections

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