Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-26T01:30:51.208Z Has data issue: false hasContentIssue false
  • English
  • Français

The role of the tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) in offspring exposed to prenatal hypoxia

Published online by Cambridge University Press:  18 December 2017

L. M. Reyes ,
A. Shah ,
A. Quon ,
J. S. Morton  and
S. T. Davidge
L. M. Reyes
Affiliation:
Department of Physiology, University of Alberta, Edmonton, AB, Canada Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB, Canada
A. Shah
Affiliation:
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB, Canada
A. Quon
Affiliation:
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada
J. S. Morton
Affiliation:
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB, Canada
S. T. Davidge*
Affiliation:
Department of Physiology, University of Alberta, Edmonton, AB, Canada Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB, Canada
*
*Address for correspondence: S. T. Davidge, Women and Children’s Health Research Institute and Departments of Obstetrics and Gynecology, and Physiology, University of Alberta, 232 HMRC Building, Edmonton, AB, Canada T6G 2S2. (Email [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Exposure to prenatal hypoxia in rats leads to intrauterine growth restriction (IUGR), decreases fetal cardiomyocyte proliferation and increases the risk to develop cardiovascular diseases (CVD) later in life. The tumor necrosis factor-related weak inducer of apoptosis (TWEAK) induces cardiomyocyte proliferation through activation of the fibroblast growth factor-inducible molecule 14 (Fn-14) receptor. The TWEAK/Fn-14 pathway becomes quiescent shortly after birth, however, it becomes upregulated with CVD; suggesting that it could be a link between the increased susceptibility to CVD in pregnancies complicated by hypoxia/IUGR. We hypothesized that offspring exposed to prenatal hypoxia will exhibit reduced cardiomyocyte proliferation due to reduced Fn-14 expression and that the TWEAK/Fn-14 pathway will be expressed in those adult offspring. We exposed pregnant Sprague Dawley rats to control (21% oxygen) or hypoxic (11% oxygen) conditions from gestational days 15 to 21. Ventricular cardiomyocytes were isolated from male and female, control and hypoxic offspring at postnatal day 1. Proliferation was assessed in the presence or absence of r-TWEAK (72 h, 100 ng/ml). Prenatal hypoxia was not associated with differences in Fn-14 protein expression in either male or female offspring. Cardiomyocytes from prenatal hypoxic male, but not female, offspring had decreased proliferation compared with controls. Addition of r-TWEAK increased cardiomyocyte proliferation in all offspring. In adult offspring of all groups, the TWEAK/Fn-14 pathway was not detectable. Cardiomyocyte proliferation was reduced in only male offspring exposed to prenatal hypoxia but this was not due to changes in the Fn-14 pathway. Studies addressing other pathways associated with CVD and prenatal hypoxia are needed.

Keywords

cardiomyocyte proliferationprenatal hypoxiaTWEAK
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 6 , December 2018 , pp. 661 - 669
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Barker, DJ, Winter, PD, Osmond, C, Margetts, B, Simmonds, SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2, 577–580.Google Scholar
2. Barker, DJ. The fetal origins of hypertension. J Hypertens Suppl. 1996; 14, S117–S120.Google Scholar
3. Barker, DJ, Gluckman, PD, Godfrey, KM, et al. Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993; 341, 938–941.Google Scholar
4. Global Status Report on Noncommunicable Diseases 2010. Global status report on noncommunicable diseases 2010. 2011, pp. 1–162.Google Scholar
5. Go, AS, Mozaffarian, D, Roger, VL, et al. Heart disease and stroke statistics – 2014 update: a report from the American Heart Association. Circulation. 2014; 129, e28–e292.Google Scholar
6. Canada PHAo. Economic burden of illness in Canada 2000. Public Health Agency of Canada. 2000 [cited 2 February 2015]. Retrieved 14 June 2012 from http://www.phac-aspc.gc.ca/cd-mc/cvd-mcv/cvd_ebic-mcv_femc-eng.php Google Scholar
7. Imdad, A, Yakoob, MY, Siddiqui, S, Bhutta, ZA. Screening and triage of intrauterine growth restriction (IUGR) in general population and high risk pregnancies: a systematic review with a focus on reduction of IUGR related stillbirths. BMC Public Health. 2011; 11(Suppl. 3), S1.Google Scholar
8. Maulik, D. Fetal growth restriction: the etiology. Clin Obstet Gynecol. 2006; 49, 228–235.Google Scholar
9. Rueda-Clausen, CF, Morton, JS, Lopaschuk, GD, Davidge, ST. Long-term effects of intrauterine growth restriction on cardiac metabolism and susceptibility to ischaemia/reperfusion. Cardiovasc Res. 2011; 90, 285–294.Google Scholar
10. Xu, Y, Williams, SJ, O’Brien, D, Davidge, ST. Hypoxia or nutrient restriction during pregnancy in rats leads to progressive cardiac remodeling and impairs postischemic recovery in adult male offspring. FASEB J. 2006; 20, 1251–1253.Google Scholar
11. Reyes, LM, Kirschenman, R, Quon, A, et al. Aerobic exercise training reduces cardiac function in adult male offspring exposed to prenatal hypoxia. Am J Physiol Regul Integr Comp Physiol. 2015; 309, R489–R498.Google Scholar
12. Tong, W, Xue, Q, Li, Y, Zhang, L. Maternal hypoxia alters matrix metalloproteinase expression patterns and causes cardiac remodeling in fetal and neonatal rats. Am J Physiol Heart Circ Physiol. 2011; 301, H2113–H2121.Google Scholar
13. Marcela, SG, Cristina, RM, Angel, PG, et al. Chronological and morphological study of heart development in the rat. Anat Rec (Hoboken). 2012; 295, 1267–1290.Google Scholar
14. Clubb, FJ Jr, Bishop, SP. Formation of binucleated myocardial cells in the neonatal rat. An index for growth hypertrophy. Lab Invest. 1984; 50, 571–577.Google Scholar
15. Bae, S, Xiao, Y, Li, G, Casiano, CA, Zhang, L. Effect of maternal chronic hypoxic exposure during gestation on apoptosis in fetal rat heart. Am J Physiol Heart Circ Physiol. 2003; 285, H983–H990.Google Scholar
16. Paradis, A, Xiao, D, Zhou, J, Zhang, L. Endothelin-1 promotes cardiomyocyte terminal differentiation in the developing heart via heightened DNA methylation. Int J Med Sci. 2014; 11, 373–380.Google Scholar
17. Sundgren, NC, Giraud, GD, Stork, PJ, Maylie, JG, Thornburg, KL. Angiotensin II stimulates hyperplasia but not hypertrophy in immature ovine cardiomyocytes. J Physiol. 2003; 548(Pt 3), 881–891.Google Scholar
18. Giraud, GD, Louey, S, Jonker, S, Schultz, J, Thornburg, KL. Cortisol stimulates cell cycle activity in the cardiomyocyte of the sheep fetus. Endocrinology. 2006; 147, 3643–3649.Google Scholar
19. Chattergoon, NN, Giraud, GD, Thornburg, KL. Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro. J Endocrinol. 2007; 192, R1–R8.Google Scholar
20. Sundgren, NC, Giraud, GD, Schultz, JM, et al. Extracellular signal-regulated kinase and phosphoinositol-3 kinase mediate IGF-1 induced proliferation of fetal sheep cardiomyocytes. Am J Physiol Regul Integr Comp Physiol. 2003; 285, R1481–R1489.Google Scholar
21. Thornburg, K, Jonker, S, O’Tierney, P, et al. Regulation of the cardiomyocyte population in the developing heart. Prog Biophys Mol Biol. 2011; 106, 289–299.Google Scholar
22. Louey, S, Jonker, SS, Giraud, GD, Thornburg, KL. Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes. J Physiol. 2007; 580(Pt 2), 639–648.Google Scholar
23. Novoyatleva, T, Diehl, F, van Amerongen, MJ, et al. TWEAK is a positive regulator of cardiomyocyte proliferation. Cardiovasc Res. 2010; 85, 681–690.Google Scholar
24. Chicheportiche, Y, Bourdon, PR, Xu, H, et al. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J Biol Chem. 1997; 272, 32401–32410.Google Scholar
25. Winkles, JA. The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting. Nat Rev Drug Discov. 2008; 7, 411–425.Google Scholar
26. Mustonen, E, Sakkinen, H, Tokola, H, et al. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 during cardiac remodelling in rats. Acta Physiol (Oxf). 2010; 199, 11–22.Google Scholar
27. Chorianopoulos, E, Heger, T, Lutz, M, et al. FGF-inducible 14-kDa protein (Fn14) is regulated via the RhoA/ROCK kinase pathway in cardiomyocytes and mediates nuclear factor-kappaB activation by TWEAK. Basic Res Cardiol. 2010; 105, 301–313.Google Scholar
28. Yang, B, Yan, P, Gong, H, et al. TWEAK protects cardiomyocyte against apoptosis in a PI3K/AKT pathway dependent manner. Am J Transl Res. 2016; 8, 3848–3860.Google Scholar
29. Reyes, LM, Morton, JS, Kirschenman, R, DeLorey, DS, Davidge, ST. Vascular effects of aerobic exercise training in rat adult offspring exposed to hypoxia-induced intrauterine growth restriction. J Physiol. 2015; 1913–1929.Google Scholar
30. Novoyatleva, T, Janssen, W, Wietelmann, A, Schermuly, RT, Engel, FB. TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy. Cytokine. 2013; 64, 43–45.Google Scholar
31. Jain, M, Jakubowski, A, Cui, L, et al. A novel role for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the development of cardiac dysfunction and failure. Circulation. 2009; 119, 2058–2068.Google Scholar
32. Rueda-Clausen, CF, Dolinsky, VW, Morton, JS, et al. Hypoxia-induced intrauterine growth restriction increases the susceptibility of rats to high-fat diet-induced metabolic syndrome. Diabetes. 2011; 60, 507–516.Google Scholar
33. Rueda-Clausen, CF, Morton, JS, Davidge, ST. Effects of hypoxia-induced intrauterine growth restriction on cardiopulmonary structure and function during adulthood. Cardiovasc Res. 2009; 81, 713–722.Google Scholar
34. Shah, A, Reyes, LM, Morton, JS, et al. Effect of resveratrol on metabolic and cardiovascular function in male and female adult offspring exposed to prenatal hypoxia and a high-fat diet. J Physiol. 2016; 594, 1465–1482.Google Scholar
35. Black, MJ, Siebel, AL, Gezmish, O, Moritz, KM, Wlodek, ME. Normal lactational environment restores cardiomyocyte number after uteroplacental insufficiency: implications for the preterm neonate. Am J Physiol Regul Integr Comp Physiol. 2012; 302, R1101–R1110.Google Scholar
36. Botting, KJ, McMillen, IC, Forbes, H, Nyengaard, JR, Morrison, JL. Chronic hypoxemia in late gestation decreases cardiomyocyte number but does not change expression of hypoxia-responsive genes. J Am Heart Assoc. 2014; 3, e000531.Google Scholar
37. Bubb, KJ, Cock, ML, Black, MJ, et al. Intrauterine growth restriction delays cardiomyocyte maturation and alters coronary artery function in the fetal sheep. J Physiol. 2007; 578(Pt 3), 871–881.Google Scholar
38. Morrison, JL, Botting, KJ, Dyer, JL, et al. Restriction of placental function alters heart development in the sheep fetus. Am J Physiol Regul Integr Comp Physiol. 2007; 293, R306–R313.Google Scholar
39. Burrell, JH, Boyn, AM, Kumarasamy, V, et al. Growth and maturation of cardiac myocytes in fetal sheep in the second half of gestation. Anat Rec A Discov Mol Cell Evol Biol. 2003; 274, 952–961.Google Scholar
40. Shi, J, Jiang, B, Qiu, Y, et al. PGC1alpha plays a critical role in TWEAK-induced cardiac dysfunction. PLoS One. 2013; 8, e54054.Google Scholar
41. Sun, L, Zhao, M, Yu, XJ, et al. Cardioprotection by acetylcholine: a novel mechanism via mitochondrial biogenesis and function involving the PGC-1alpha pathway. J Cell Physiol. 2013; 228, 1238–1248.Google Scholar
42. Gerdes, J, Lemke, H, Baisch, H, et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984; 133, 1710–1715.Google Scholar
43. Gratzner, HG. Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: a new reagent for detection of DNA replication. Science. 1982; 218, 474–475.Google Scholar
44. van Dierendonck, JH, Wijsman, JH, Keijzer, R, van de Velde, CJ, Cornelisse, CJ. Cell-cycle-related staining patterns of anti-proliferating cell nuclear antigen monoclonal antibodies. Comparison with BrdUrd labeling and Ki-67 staining. Am J Pathol. 1991; 138, 1165–1172.Google Scholar
45. Drewinko, B, Yang, LY, Barlogie, B, Trujillo, JM. Cultured human tumour cells may be arrested in all stages of the cycle during stationary phase: demonstration of quiescent cells in G1, S and G2 phase. Cell Tissue Kinet. 1984; 17, 453–463.Google Scholar
46. Scholzen, T, Gerdes, J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000; 182, 311–322.Google Scholar
47. Cohen, E, Wong, FY, Horne, RS, Yiallourou, SR. Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy. Pediatr Res. 2016; 79, 821–830.Google Scholar
48. Murphy, PJ. The fetal circulation. Continuing Education in Anaesthesia, Critical Care & Pain. 2005; 5, 107–112.Google Scholar
49. Baschat, AA. Fetal responses to placental insufficiency: an update. BJOG. 2004; 111, 1031–1041.Google Scholar