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Small size at birth predicts decreased cardiomyocyte number in the adult ovine heart

Published online by Cambridge University Press:  15 May 2017

S. Vranas ,
G. K. Heinemann ,
H. Liu ,
M. J. De Blasio ,
J. A. Owens ,
K. L. Gatford Open the ORCID record for K. L. Gatford [Opens in a new window]  and
M. J. Black
S. Vranas
Affiliation:
Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
G. K. Heinemann
Affiliation:
Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
H. Liu
Affiliation:
Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
M. J. De Blasio
Affiliation:
Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
J. A. Owens
Affiliation:
Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
K. L. Gatford*
Affiliation:
Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
M. J. Black
Affiliation:
Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
*
*Address for correspondence: Dr K. L. Gatford, Robinson Research Institute and Adelaide Medical School, Adelaide, SA 5005, Australia. (Email: kathy.gatford@adelaide.edu.au)
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Abstract

Low birth weight is associated with increased risk of cardiovascular disease in adulthood. Intrauterine growth restriction (IUGR) hearts have fewer CMs in early postnatal life, which may impair postnatal cardiovascular function and hence, explain increased disease risk, but whether the cardiomyocyte deficit persists to adult life is unknown. We therefore studied the effects of experimentally induced placental restriction (PR) on cardiac outcomes in young adult sheep. Heart size, cardiomyocyte number, nuclearity and size were measured in control (n=5) and PR (n=5) male sheep at 1 year of age. PR lambs were 36% lighter at birth (P=0.007), had 38% faster neonatal relative growth rates (P=0.001) and had 21% lighter heart weights relative to body weight as adults (P=0.024) than control lambs. Cardiomyocyte number, nuclearity and size in the left ventricle did not differ between control and PR adults; hearts of both groups contained cardiomyocytes (CM) with between one and four nuclei. Overall, cardiomyocyte number in the adult left ventricle correlated positively with birth weight but not with adult weight. This study is the first to demonstrate that intrauterine growth directly influences the complement of CM in the adult heart. Cardiomyocyte size was not correlated with cardiomyocyte number or birth weight. Our results suggest that body weight at birth affects lifelong cardiac functional reserve. We hypothesise that decreased cardiomyocyte number of low birth weight individuals may impair their capacity to adapt to additional challenges such as obesity and ageing.

Keywords

birth weightcardiomyocyteheartIUGRsheep
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 5: Themed Issue: Australian Perspectives: Outcomes from the 2016 ANZ , October 2017 , pp. 618 - 625
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

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Footnotes

a

Present address: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.

b

Present address: Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.

†

K.L. Gatford and M.J. Black are joint senior authors.

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