Fetal Origins of Adult Cardiac Disease: a Novel Approach to Prevent Fetal Growth Restriction Induced Cardiac Dysfunction Using Insulin Like Growth Factor

Overview

Journal Pediatr Res

Specialties Biology
Pediatrics

Date 2017 Jan 19

PMID 28099426

Citations 8

Authors

Tarek Alsaied

Khaled Omar

Jeanne F James

Robert B Hinton

Timothy M Crombleholme

Mounira Habli

Affiliations

Soon will be listed here.

Abstract

Background: Fetal growth restriction (FGR) is a risk factor for adult cardiovascular disease. Intraplacental gene transfer of human insulin-like growth factor-1 (IGF-1) corrects birth weight in our mouse model of FGR. This study addresses long term effects of FGR on cardiac function and the potential preventive effect of IGF-1.

Study Design: Laparotomy was performed on pregnant C57BL/6J mice at embryonic day 18 and pups were divided into three groups: Sham operated; FGR (induced by mesenteric uterine artery ligation); treatment (intraplacental injection of IGF-1 after uterine artery ligation). Pups were followed until 32 wk of life. Transthoracic echocardiography was performed starting at 12 wk.

Results: Systolic cardiac function was significantly impaired in the FGR group with reduced fractional shortening compared with sham and treatment group starting at week 12 of life (20 ± 4 vs. 31 ± 5 vs. 32 ± 5, respectively, n = 12 for each group; P < 0.001) with no difference between the sham and treatment groups.

Conclusion: Intraplacental gene transfer of IGF-1 prevents FGR induced cardiac dysfunction. This suggests that in utero therapy may positively impact cardiac remodeling and prevent adult cardiovascular disease.

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References

Ellison G, Torella D, Dellegrottaglie S, Perez-Martinez C, de Prado A, Vicinanza C . Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart. J Am Coll Cardiol. 2011; 58(9):977-86. DOI: 10.1016/j.jacc.2011.05.013. View

Barker D, Osmond C, Golding J, Kuh D, Wadsworth M . Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989; 298(6673):564-7. PMC: 1835925. DOI: 10.1136/bmj.298.6673.564. View

Crispi F, Bijnens B, Figueras F, Bartrons J, Eixarch E, le Noble F . Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation. 2010; 121(22):2427-36. DOI: 10.1161/CIRCULATIONAHA.110.937995. View

Eriksson J . Early growth and coronary heart disease and type 2 diabetes: findings from the Helsinki Birth Cohort Study (HBCS). Am J Clin Nutr. 2011; 94(6 Suppl):1799S-1802S. DOI: 10.3945/ajcn.110.000638. View

Menendez-Castro C, Toka O, Fahlbusch F, Cordasic N, Wachtveitl R, Hilgers K . Impaired myocardial performance in a normotensive rat model of intrauterine growth restriction. Pediatr Res. 2014; 75(6):697-706. DOI: 10.1038/pr.2014.27. View

Sehgal A, Doctor T, Menahem S . Cardiac function and arterial biophysical properties in small for gestational age infants: postnatal manifestations of fetal programming. J Pediatr. 2013; 163(5):1296-300. DOI: 10.1016/j.jpeds.2013.06.030. View

Rueda-Clausen C, Morton J, Lopaschuk G, Davidge S . Long-term effects of intrauterine growth restriction on cardiac metabolism and susceptibility to ischaemia/reperfusion. Cardiovasc Res. 2010; 90(2):285-94. DOI: 10.1093/cvr/cvq363. View

Eremia S, de Boo H, Bloomfield F, Oliver M, Harding J . Fetal and amniotic insulin-like growth factor-I supplements improve growth rate in intrauterine growth restriction fetal sheep. Endocrinology. 2007; 148(6):2963-72. DOI: 10.1210/en.2006-1701. View

Habli M, Jones H, Aronow B, Omar K, Crombleholme T . Recapitulation of characteristics of human placental vascular insufficiency in a novel mouse model. Placenta. 2013; 34(12):1150-8. DOI: 10.1016/j.placenta.2013.09.011. View

10.

Ozanne S, Lewis R, Jennings B, Hales C . Early programming of weight gain in mice prevents the induction of obesity by a highly palatable diet. Clin Sci (Lond). 2003; 106(2):141-5. DOI: 10.1042/CS20030278. View

11.

Tude Rodrigues A, Hataishi R, Ichinose F, Bloch K, Derumeaux G, Picard M . Relationship of systolic dysfunction to area at risk and infarction size after ischemia-reperfusion in mice. J Am Soc Echocardiogr. 2004; 17(9):948-53. DOI: 10.1016/j.echo.2004.05.014. View

12.

Touvron M, Escoubet B, Mericskay M, Angelini A, Lamotte L, Santini M . Locally expressed IGF1 propeptide improves mouse heart function in induced dilated cardiomyopathy by blocking myocardial fibrosis and SRF-dependent CTGF induction. Dis Model Mech. 2012; 5(4):481-91. PMC: 3380711. DOI: 10.1242/dmm.009456. View

13.

Yoon P, Bastian B, Anderson R, Collins J, Jaffe H . Potentially preventable deaths from the five leading causes of death--United States, 2008-2010. MMWR Morb Mortal Wkly Rep. 2014; 63(17):369-74. PMC: 4584887. View

14.

Keswani S, Balaji S, Katz A, King A, Omar K, Habli M . Intraplacental gene therapy with Ad-IGF-1 corrects naturally occurring rabbit model of intrauterine growth restriction. Hum Gene Ther. 2015; 26(3):172-82. PMC: 4367241. DOI: 10.1089/hum.2014.065. View

15.

Demicheva E, Crispi F . Long-term follow-up of intrauterine growth restriction: cardiovascular disorders. Fetal Diagn Ther. 2013; 36(2):143-53. DOI: 10.1159/000353633. View

16.

Lim K, Lombardo P, Schneider-Kolsky M, Black M . Intrauterine growth restriction coupled with hyperglycemia: effects on cardiac structure in adult rats. Pediatr Res. 2012; 72(4):344-51. DOI: 10.1038/pr.2012.94. View

17.

Cox B, Kotlyar M, Evangelou A, Ignatchenko V, Ignatchenko A, Whiteley K . Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology. Mol Syst Biol. 2009; 5:279. PMC: 2710868. DOI: 10.1038/msb.2009.37. View

18.

Puche J, Castilla-Cortazar I . Human conditions of insulin-like growth factor-I (IGF-I) deficiency. J Transl Med. 2012; 10:224. PMC: 3543345. DOI: 10.1186/1479-5876-10-224. View

19.

Bahtiyar M, Copel J . Cardiac changes in the intrauterine growth-restricted fetus. Semin Perinatol. 2008; 32(3):190-3. DOI: 10.1053/j.semperi.2008.02.010. View

20.

Ren J, Samson W, Sowers J . Insulin-like growth factor I as a cardiac hormone: physiological and pathophysiological implications in heart disease. J Mol Cell Cardiol. 1999; 31(11):2049-61. DOI: 10.1006/jmcc.1999.1036. View