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Fibroblast Growth Factor-2 regulates proliferation of cardiac myocytes in normal and hypoplastic left ventricles in the developing chick

Published online by Cambridge University Press:  01 April 2009

Angela deAlmeida  and
David Sedmera
Angela deAlmeida
Affiliation:
Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina, United States of America
David Sedmera*
Affiliation:
Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina, United States of America Institute of Anatomy, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic Institute of Animal Physiology and Genetics and Institute of Physiology (Centre for Cardiovascular Research), Academy of Sciences of the Czech Republic, Prague, Czech Republic
*
Correspondence to: David Sedmera, Institute of Anatomy, 1st Faculty of Medicine, Charles University in Prague, U Nemocnice 3, 128 00 Prague 2, Czech Republic. Phone:+420 224 965 941; Fax: +420 224 965 770; E-mail: [email protected]
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Abstract

The developing heart increases its mass predominantly by increasing the number of contained cells through proliferation. We hypothesized that addition of fibroblast growth factor-2, a factor previously shown to stimulate division of the embryonic myocytes, to the left ventricular myocardium in an experimental model of left heart hypoplasia created in the chicken would attenuate phenotypic severity by increasing cellular proliferation. We have established an effective mode of delivery of fibroblast growth factor-2 to the chick embryonic left ventricular myocardium by using adenovirus vectors, which was more efficient and better tolerated than direct injection of recombinant fibroblast growth factor-2 protein. Injection of control adenovirus expressing green fluorescent protein did not result in significant alterations in myocytic proliferation or cell death compared with intact, uninjected, controls. Co-injection of adenoviruses expressing green fluorescent protein and fibroblast growth factor-2 was used for verification of positive injection, and induction of proliferation, respectively. Treatment of both normal and hypoplastic left ventricles with fibroblast growth factor-2 expressing adenovirus resulted in to 2 to 3-fold overexpression of fibroblast growth factor-2, as verified by immunostaining. An increase by 45% in myocytic proliferation was observed following injection of normal hearts, and an increase of 39% was observed in hypoplastic hearts. There was a significant increase in anti-myosin immunostaining in the hypoplastic, but not the normal hearts. We have shown, therefore, that expression of exogenous fibroblast growth factor-2 in the late embryonic heart can exert direct effects on cardiac myocytes, inducing both their proliferation and differentiation. These data suggest potential for a novel therapeutic option in selected cases of congenital cardiac disease, such as hypoplastic left heart syndrome.

Keywords

Chick embryohypoplastic left heart syndromeadenoviruscardiomyocyte
Type
Original Article
Information
Cardiology in the Young , Volume 19 , Issue 2 , April 2009 , pp. 159 - 169
Copyright
Copyright © Cambridge University Press 2009

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