Skip to main content

Advertisement

SpringerLink
Log in

Prenatal Alcohol Exposure Causes Adverse Cardiac Extracellular Matrix Changes and Dysfunction in Neonatal Mice

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Fetal alcohol syndrome (FAS) is the most severe condition of fetal alcohol spectrum disorders (FASD) and is associated with congenital heart defects. However, more subtle defects such as ventricular wall thinning and cardiac compliance may be overlooked in FASD. Our studies focus on the role of cardiac fibroblasts in the neonatal heart, and how they are affected by prenatal alcohol exposure (PAE). We hypothesize that PAE affects fibroblast function contributing to dysregulated collagen synthesis, which leads to cardiac dysfunction. To investigate these effects, pregnant C57/BL6 mice were intraperitoneally injected with 2.9 g EtOH/kg dose to achieve a blood alcohol content of approximately 0.35 on gestation days 6.75 and 7.25. Pups were sacrificed on neonatal day 5 following echocardiography measurements of left ventricular (LV) chamber dimension and function. Hearts were used for primary cardiac fibroblast isolation or protein expression analysis. PAE animals had thinner ventricular walls than saline exposed animals, which was associated with increased LV wall stress and decreased ejection fraction. In isolated fibroblasts, PAE decreased collagen I/III ratio and increased gene expression of profibrotic markers, including α-smooth muscle actin and lysyl oxidase. Notch1 signaling was assessed as a possible mechanism for fibroblast activation, and indicated that gene expression of Notch1 receptor and downstream Hey1 transcription factor were increased. Cardiac tissue analysis revealed decreased collagen I/III ratio and increased protein expression of α-smooth muscle actin and lysyl oxidase. However, Notch1 signaling components decreased in whole heart tissue. Our study demonstrates that PAE caused adverse changes in the cardiac collagen profile and a decline in cardiac function in the neonatal heart.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Jones, K. L. (2011). The effects of alcohol on fetal development. Birth Defects Research Part C: Embryo Today, 93(1), 3–11. https://doi.org/10.1002/bdrc.20200.

    Article  CAS  PubMed  Google Scholar 

  2. Floyd, R. L., & Sidhu, J. S. (2004). Monitoring prenatal alcohol exposure. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 127C(1), 3–9. https://doi.org/10.1002/ajmg.c.30010.

    Article  Google Scholar 

  3. Karunamuni, G., Gu, S., Doughman, Y. Q., Peterson, L. M., Mai, K., McHale, Q., et al. (2014). Ethanol exposure alters early cardiac function in the looping heart: A mechanism for congenital heart defects? American Journal of Physiology-Heart and Circulatory Physiology, 306(3), H414–H421. https://doi.org/10.1152/ajpheart.00600.2013.

    Article  CAS  PubMed  Google Scholar 

  4. Tan, C. H., Denny, C. H., Cheal, N. E., Sniezek, J. E., & Kanny, D. (2015). Alcohol use and binge drinking among women of childbearing age—United States, 2011–2013. MMWR Morbidity and Mortality Weekly Report, 64(37), 1042–1046. https://doi.org/10.15585/mmwr.mm6437a3.

    Article  PubMed  Google Scholar 

  5. Finer, L. B., & Henshaw, S. K. (2006). Disparities in rates of unintended pregnancy in the United States, 1994 and 2001. Perspectives on Sexual and Reproductive Health, 38(2), 90–96. https://doi.org/10.1363/psrh.38.090.06.

    Article  PubMed  Google Scholar 

  6. Trussell, J., Lalla, A. M., Doan, Q. V., Reyes, E., Pinto, L., & Gricar, J. (2009). Cost effectiveness of contraceptives in the United States. Contraception, 79(1), 5–14. https://doi.org/10.1016/j.contraception.2008.08.003.

    Article  PubMed  Google Scholar 

  7. Naimi, T. S., Lipscomb, L. E., Brewer, R. D., & Gilbert, B. C. (2003). Binge drinking in the preconception period and the risk of unintended pregnancy: Implications for women and their children. Pediatrics, 111(5 Pt 2), 1136–1141.

    PubMed  Google Scholar 

  8. Linask, K. K., & Han, M. (2016). Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention. Birth Defects Research Part A: Clinical and Molecular Teratology, 106(9), 749–760. https://doi.org/10.1002/bdra.23526.

    Article  CAS  PubMed  Google Scholar 

  9. Iveli, M. F., Morales, S., Rebolledo, A., Savietto, V., Salemme, S., Apezteguia, M., et al. (2007). Effects of light ethanol consumption during pregnancy: Increased frequency of minor anomalies in the newborn and altered contractility of umbilical cord artery. Pediatric Research, 61(4), 456–461. https://doi.org/10.1203/pdr.0b013e3180332c59.

    Article  CAS  PubMed  Google Scholar 

  10. Loser, H., & Majewski, F. (1977). Type and frequency of cardiac defects in embryofetal alcohol syndrome. Report of 16 cases. British Heart Journal, 39(12), 1374–1379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Burd, L., Deal, E., Rios, R., Adickes, E., Wynne, J., & Klug, M. G. (2007). Congenital heart defects and fetal alcohol spectrum disorders. Congenital Heart Disease, 2(4), 250–255. https://doi.org/10.1111/j.1747-0803.2007.00105.x.

    Article  PubMed  Google Scholar 

  12. Serrano, M., Han, M., Brinez, P., & Linask, K. K. (2010). Fetal alcohol syndrome: Cardiac birth defects in mice and prevention with folate. American Journal of Obstetrics and Gynecology, 203(1), 75-e7. https://doi.org/10.1016/j.ajog.2010.03.017.

    Article  CAS  Google Scholar 

  13. Parkington, H. C., Coleman, H. A., Wintour, E. M., & Tare, M. (2010). Prenatal alcohol exposure: Implications for cardiovascular function in the fetus and beyond. Clinical and Experimental Pharmacology and Physiology, 37(2), e91–e98. https://doi.org/10.1111/j.1440-1681.2009.05342.x.

    Article  CAS  PubMed  Google Scholar 

  14. Gray, S. P., Denton, K. M., Cullen-McEwen, L., Bertram, J. F., & Moritz, K. M. (2010). Prenatal exposure to alcohol reduces nephron number and raises blood pressure in progeny. Journal of the American Society of Nephrology, 21(11), 1891–1902. https://doi.org/10.1681/ASN.2010040368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Turcotte, L. A., Aberle, N. S., Norby, F. L., Wang, G. J., & Ren, J. (2002). Influence of prenatal ethanol exposure on vascular contractile response in rat thoracic aorta. Alcohol, 26(2), 75–81.

    Article  CAS  PubMed  Google Scholar 

  16. Lockhart, M., Wirrig, E., Phelps, A., & Wessels, A. (2011). Extracellular matrix and heart development. Birth Defects Research Part A—Clinical and Molecular Teratology, 91(6), 535–550. https://doi.org/10.1002/bdra.20810.

    Article  CAS  Google Scholar 

  17. Deb, A., & Ubil, E. (2014). Cardiac fibroblast in development and wound healing. Journal of Molecular and Cellular Cardiology, 70, 47–55. https://doi.org/10.1016/j.yjmcc.2014.02.017.

    Article  CAS  PubMed  Google Scholar 

  18. Souders, C. A., Bowers, S. L., & Baudino, T. A. (2009). Cardiac fibroblast: The renaissance cell. Circulation Research, 105(12), 1164–1176. https://doi.org/10.1161/CIRCRESAHA.109.209809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gershlak, J. R., Resnikoff, J. I., Sullivan, K. E., Williams, C., Wang, R. M., & Black, L. D. 3rd (2013). Mesenchymal stem cells ability to generate traction stress in response to substrate stiffness is modulated by the changing extracellular matrix composition of the heart during development. Biochemical and Biophysical Research Communications, 439(2), 161–166. https://doi.org/10.1016/j.bbrc.2013.08.074.

    Article  CAS  PubMed  Google Scholar 

  20. Katsumi, A., Orr, A. W., Tzima, E., & Schwartz, M. A. (2004). Integrins in mechanotransduction. Journal of Biological Chemistry, 279(13), 12001–12004. https://doi.org/10.1074/jbc.R300038200.

    Article  CAS  Google Scholar 

  21. Baudino, T. A., Carver, W., Giles, W., & Borg, T. K. (2006). Cardiac fibroblasts: Friend or foe? American Journal of Physiology: Heart and Circulatory Physiology, 291(3), H1015–H1026. https://doi.org/10.1152/ajpheart.00023.2006.

    Article  CAS  PubMed  Google Scholar 

  22. Leask, A. (2010). Potential therapeutic targets for cardiac fibrosis: TGFbeta, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation. Circulation Research, 106(11), 1675–1680. https://doi.org/10.1161/CIRCRESAHA.110.217737.

    Article  CAS  PubMed  Google Scholar 

  23. El Hajj, E. C., El Hajj, M. C., Voloshenyuk, T. G., Mouton, A. J., Khoutorova, E., Molina, P. E., et al. (2014). Alcohol modulation of cardiac matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs favors collagen accumulation. Alcoholism: Clinical and Experimental Research, 38(2), 448–456. https://doi.org/10.1111/acer.12239.

    Article  CAS  Google Scholar 

  24. Law, B. A., & Carver, W. E. (2013). Activation of cardiac fibroblasts by ethanol is blocked by TGF-beta inhibition. Alcoholism: Clinical and Experimental Research, 37(8), 1286–1294. https://doi.org/10.1111/acer.12111.

    Article  CAS  Google Scholar 

  25. Oswald, F., Tauber, B., Dobner, T., Bourteele, S., Kostezka, U., Adler, G., et al. (2001). p300 acts as a transcriptional coactivator for mammalian Notch-1. Molecular Cell Biology, 21(22), 7761–7774. https://doi.org/10.1128/MCB.21.22.7761-7774.2001.

    Article  CAS  Google Scholar 

  26. Dettman, R. W., Denetclaw, W. Jr., Ordahl, C. P., & Bristow, J. (1998). Common epicardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart. Developmental Biology, 193(2), 169–181. https://doi.org/10.1006/dbio.1997.8801.

    Article  CAS  PubMed  Google Scholar 

  27. Vrancken Peeters, M. P., Gittenberger-de Groot, A. C., Mentink, M. M., & Poelmann, R. E. (1999). Smooth muscle cells and fibroblasts of the coronary arteries derive from epithelial-mesenchymal transformation of the epicardium. Anatomy and Embryology (Berlin), 199(4), 367–378.

    Article  CAS  Google Scholar 

  28. Grego-Bessa, J., Luna-Zurita, L., del Monte, G., Bolos, V., Melgar, P., Arandilla, A., et al. (2007). Notch signaling is essential for ventricular chamber development. Developmental Cell, 12(3), 415–429. https://doi.org/10.1016/j.devcel.2006.12.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Xing, Y., Bai, R. Y., Yan, W. H., Han, X. F., Duan, P., Xu, Y., et al. (2007). Expression changes of Notch-related genes during the differentiation of human mesenchymal stem cells into neurons. Sheng Li Xue Bao, 59(3), 267–272.

    CAS  PubMed  Google Scholar 

  30. Timmerman, L. A., Grego-Bessa, J., Raya, A., Bertran, E., Perez-Pomares, J. M., Diez, J., et al. (2004). Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes & Development, 18(1), 99–115. https://doi.org/10.1101/gad.276304.

    Article  CAS  Google Scholar 

  31. Forsyth, C. B., Shaikh, M., Bishehsari, F., Swanson, G., Voigt, R. M., Dodiya, H., et al. (2017). Alcohol feeding in mice promotes colonic hyperpermeability and changes in colonic organoid stem cell fate. Alcoholism: Clinical and Experimental Research, 41(12), 2100–2113. https://doi.org/10.1111/acer.13519.

    Article  CAS  Google Scholar 

  32. Khayrullin, A., Smith, L., Mistry, D., Dukes, A., Pan, Y. A., & Hamrick, M. W. (2016). Chronic alcohol exposure induces muscle atrophy (myopathy) in zebrafish and alters the expression of microRNAs targeting the Notch pathway in skeletal muscle. Biochemical and Biophysical Research Communications, 479(3), 590–595. https://doi.org/10.1016/j.bbrc.2016.09.117.

    Article  CAS  PubMed  Google Scholar 

  33. Ninh, V. K., El Hajj, E. C., Mouton, A. J., El Hajj, M. C., Gilpin, N. W., & Gardner, J. D. (2018). Chronic ethanol administration prevents compensatory cardiac hypertrophy in pressure overload. Alcoholism: Clinical and Experimental Research. https://doi.org/10.1111/acer.13799.

    Article  Google Scholar 

  34. Hutchinson, K. R., Guggilam, A., Cismowski, M. J., Galantowicz, M. L., West, T. A., Stewart, J. A. Jr., et al. (2011). Temporal pattern of left ventricular structural and functional remodeling following reversal of volume overload heart failure. Journal of Applied Physiology (1985), 111(6), 1778–1788. https://doi.org/10.1152/japplphysiol.00691.2011.

    Article  CAS  PubMed Central  Google Scholar 

  35. Hoyme, H. E., Kalberg, W. O., Elliott, A. J., Blankenship, J., Buckley, D., Marais, A. S., et al. (2016). Updated clinical guidelines for diagnosing fetal alcohol spectrum disorders. Pediatrics, 138(2), e20154256. https://doi.org/10.1542/peds.2015-4256.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Rojmahamongkol, P., Cheema-Hasan, A., & Weitzman, C. (2015). Do pediatricians recognize fetal alcohol spectrum disorders in children with developmental and behavioral problems? Journal of Developmental and Behavioral Pediatrics, 36(3), 197–202. https://doi.org/10.1097/DBP.0000000000000146.

    Article  PubMed  Google Scholar 

  37. May, P. A., Chambers, C. D., Kalberg, W. O., Zellner, J., Feldman, H., Buckley, D., et al. (2018). Prevalence of fetal alcohol spectrum disorders in 4 US Communities. JAMA, 319(5), 474–482. https://doi.org/10.1001/jama.2017.21896.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Cavieres, M. F., & Smith, S. M. (2000). Genetic and developmental modulation of cardiac deficits in prenatal alcohol exposure. Alcoholism: Clinical and Experimental Research, 24(1), 102–109.

    Article  CAS  Google Scholar 

  39. Bertrand, J., Floyd, L. L., & Weber, M. K., Fetal Alcohol Syndrome Prevention Team DoBD, Developmental Disabilities NCoBD, Developmental Disabilities CfDC, et al. (2005). Guidelines for identifying and referring persons with fetal alcohol syndrome. MMWR Recommendations and Reports, 54(RR-11), 1–14.

    PubMed  Google Scholar 

  40. Krishnan, A., Samtani, R., Dhanantwari, P., Lee, E., Yamada, S., Shiota, K., et al. (2014). A detailed comparison of mouse and human cardiac development. Pediatric Research, 76(6), 500–507. https://doi.org/10.1038/pr.2014.128.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Buckingham, M., Meilhac, S., & Zaffran, S. (2005). Building the mammalian heart from two sources of myocardial cells. Nature Reviews Genetics, 6(11), 826–835. https://doi.org/10.1038/nrg1710.

    Article  CAS  PubMed  Google Scholar 

  42. Santini, M. P., Forte, E., Harvey, R. P., & Kovacic, J. C. (2016). Developmental origin and lineage plasticity of endogenous cardiac stem cells. Development, 143(8), 1242–1258. https://doi.org/10.1242/dev.111591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Martinsen, B. J., et al. (2005) Cardiac development. In P. A. Iaizzo (Ed.), Handbook of cardiac anatomy, physiology, and devices (pp. 15–23). New Jersey: Humana Press.

    Chapter  Google Scholar 

  44. Daft, P. A., Johnston, M. C., & Sulik, K. K. (1986). Abnormal heart and great vessel development following acute ethanol exposure in mice. Teratology, 33(1), 93–104. https://doi.org/10.1002/tera.1420330112.

    Article  CAS  PubMed  Google Scholar 

  45. Naimi, T., Brewer, B., Mokdad, A., Denny, C., Serdula, M., & Marks, J. (2003). Definitions of binge drinking. JAMA, 289(13), 1635–1636. https://doi.org/10.1001/jama.289.13.1635.

    Article  Google Scholar 

  46. Perhonen, M. A., Franco, F., Lane, L. D., Buckey, J. C., Blomqvist, C. G., Zerwekh, J. E., et al. (2001). Cardiac atrophy after bed rest and spaceflight. Journal of Applied Physiology (1985), 91(2), 645–653. https://doi.org/10.1152/jappl.2001.91.2.645.

    Article  CAS  Google Scholar 

  47. Razeghi, P., Baskin, K. K., Sharma, S., Young, M. E., Stepkowski, S., Essop, M. F., et al. (2006). Atrophy, hypertrophy, and hypoxemia induce transcriptional regulators of the ubiquitin proteasome system in the rat heart. Biochemical and Biophysical Research Communications, 342(2), 361–364. https://doi.org/10.1016/j.bbrc.2006.01.163.

    Article  CAS  PubMed  Google Scholar 

  48. Razeghi, P., & Taegtmeyer, H. (2006). Hypertrophy and atrophy of the heart: The other side of remodeling. Proceedings of the National Academy of Sciences of the United States of America, 1080, 110–119. https://doi.org/10.1196/annals.1380.011.

    Article  CAS  Google Scholar 

  49. Capasso, J. M., Li, P., Guideri, G., & Anversa, P. (1991). Left ventricular dysfunction induced by chronic alcohol ingestion in rats. American Journal of Physiology, 261(1 Pt 2), H212–H219. https://doi.org/10.1152/ajpheart.1991.261.1.H212.

    Article  CAS  Google Scholar 

  50. Capasso, J. M., Li, P., Guideri, G., Malhotra, A., Cortese, R., & Anversa, P. (1992). Myocardial mechanical, biochemical, and structural alterations induced by chronic ethanol ingestion in rats. Circulation Research, 71(2), 346–356.

    Article  CAS  PubMed  Google Scholar 

  51. Drazner, M. H. (2011). The progression of hypertensive heart disease. Circulation, 123(3), 327–334. https://doi.org/10.1161/CIRCULATIONAHA.108.845792.

    Article  PubMed  Google Scholar 

  52. Lorell, B. H., & Carabello, B. A. (2000). Left ventricular hypertrophy: Pathogenesis, detection, and prognosis. Circulation, 102(4), 470–479.

    Article  CAS  PubMed  Google Scholar 

  53. Wold, L. E., Norby, F. L., Hintz, K. K., Colligan, P. B., Epstein, P. N., & Ren, J. (2001). Prenatal ethanol exposure alters ventricular myocyte contractile function in the offspring of rats: Influence of maternal Mg2+ supplementation. Cardiovascular Toxicology, 1(3), 215–224.

    Article  CAS  PubMed  Google Scholar 

  54. Ren, J., Wold, L. E., Natavio, M., Ren, B. H., Hannigan, J. H., & Brown, R. A. (2002). Influence of prenatal alcohol exposure on myocardial contractile function in adult rat hearts: Role of intracellular calcium and apoptosis. Alcohol Alcohol, 37(1), 30–37.

    Article  CAS  PubMed  Google Scholar 

  55. Russell, J. L., Goetsch, S. C., Gaiano, N. R., Hill, J. A., Olson, E. N., & Schneider, J. W. (2011). A dynamic notch injury response activates epicardium and contributes to fibrosis repair. Circulation Research, 108(1), 51–59. https://doi.org/10.1161/CIRCRESAHA.110.233262.

    Article  CAS  PubMed  Google Scholar 

  56. Fan, X., Yao, Y., & Zhang, Y. (2018). Calreticulin promotes proliferation and extracellular matrix expression through Notch pathway in cardiac fibroblasts. Advances in Clinical and Experimental Medicine. https://doi.org/10.17219/acem/74430.

    Article  PubMed  Google Scholar 

  57. Aoyagi-Ikeda, K., Maeno, T., Matsui, H., Ueno, M., Hara, K., Aoki, Y., et al. (2011). Notch induces myofibroblast differentiation of alveolar epithelial cells via transforming growth factor-{beta}-Smad3 pathway. American Journal of Respiratory Cell and Molecular Biology, 45(1), 136–144. https://doi.org/10.1165/rcmb.2010-0140OC10.1165/rcmb.2009-0140OC.

    Article  CAS  PubMed  Google Scholar 

  58. Zeisberg, E. M., Tarnavski, O., Zeisberg, M., Dorfman, A. L., McMullen, J. R., Gustafsson, E., et al. (2007). Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nature Medicine, 13(8), 952–961. https://doi.org/10.1038/nm1613.

    Article  CAS  PubMed  Google Scholar 

  59. Morrow, D., Cullen, J. P., Liu, W., Cahill, P. A., & Redmond, E. M. (2010). Alcohol inhibits smooth muscle cell proliferation via regulation of the Notch signaling pathway. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(12), 2597–2603. https://doi.org/10.1161/ATVBAHA.110.215681.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Morrow, D., Cullen, J. P., Cahill, P. A., & Redmond, E. M. (2008). Ethanol stimulates endothelial cell angiogenic activity via a Notch- and angiopoietin-1-dependent pathway. Cardiovascular Research, 79(2), 313–321. https://doi.org/10.1093/cvr/cvn108.

    Article  CAS  PubMed  Google Scholar 

  61. Sarmah, S., Muralidharan, P., & Marrs, J. A. (2016). Embryonic ethanol exposure dysregulates BMP and notch signaling, leading to persistent atrio-ventricular valve defects in Zebrafish. PLoS ONE, 11(8), e0161205. https://doi.org/10.1371/journal.pone.0161205.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Bolos, V., Grego-Bessa, J., & de la Pompa, J. L. (2007). Notch signaling in development and cancer. Endocrine Reviews, 28(3), 339–363. https://doi.org/10.1210/er.2006-0046.

    Article  CAS  PubMed  Google Scholar 

  63. Boopathy, A. V., Pendergrass, K. D., Che, P. L., Yoon, Y. S., & Davis, M. E. (2013). Oxidative stress-induced Notch1 signaling promotes cardiogenic gene expression in mesenchymal stem cells. Stem Cell Research & Therapy, 4(2), 43. https://doi.org/10.1186/scrt190.

    Article  CAS  Google Scholar 

  64. Noseda, M., Fu, Y., Niessen, K., Wong, F., Chang, L., McLean, G., et al. (2006). Smooth Muscle alpha-actin is a direct target of Notch/CSL. Circulation Research, 98(12), 1468–1470. https://doi.org/10.1161/01.RES.0000229683.81357.26.

    Article  CAS  PubMed  Google Scholar 

  65. Niessen, K., & Karsan, A. (2008). Notch signaling in cardiac development. Circulation Research, 102(10), 1169–1181. https://doi.org/10.1161/CIRCRESAHA.108.174318.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Saving Tiny Hearts Society (JDG); T32AA007577-19 (Patricia E. Molina); 1F31HL134263 (ECE).

Author information

Authors and Affiliations

  1. Department of Physiology, LSU Health Sciences Center, 1901 Perdido Street, New Orleans, LA, 70112, USA

    Van K. Ninh, Elia C. El Hajj, Alan J. Mouton & Jason D. Gardner

Authors
  1. Van K. Ninh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elia C. El Hajj
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan J. Mouton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jason D. Gardner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jason D. Gardner.

Additional information

Handling Editor: Yu-Ming Kang.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ninh, V.K., El Hajj, E.C., Mouton, A.J. et al. Prenatal Alcohol Exposure Causes Adverse Cardiac Extracellular Matrix Changes and Dysfunction in Neonatal Mice. Cardiovasc Toxicol 19, 389–400 (2019). https://doi.org/10.1007/s12012-018-09503-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-018-09503-8

Keywords

Search

Navigation