DOI QR코드

DOI QR Code

Quantification of endothelin-1 in human umbilical venous endothelial cell culture supernatants of small for gestational age and preeclampsia neonates

부당 경량아 및 전자간증 산모의 신생아 제대혈관내피세포의 endothelin-1 발현 비교

  • Cho, Won Kyoung (Department of Pediatrics, College of Medicine, Catholic University) ;
  • Kim, So Young (Department of Pediatrics, College of Medicine, Catholic University) ;
  • Chun, Chung Sik (Department of Pediatrics, College of Medicine, Catholic University)
  • 조원경 (가톨릭대학교 의과대학 소아과학교실) ;
  • 김소영 (가톨릭대학교 의과대학 소아과학교실) ;
  • 전정식 (가톨릭대학교 의과대학 소아과학교실)
  • Received : 2007.10.22
  • Accepted : 2007.11.27
  • Published : 2007.12.15

Abstract

Purpose : It was generally accepted now a days that the pathogenesis of preeclampsia, small for gestational age (SGA), intrauterine growth retardation and fetal origin of adult diseases were related with a endothelial cell dysfunction. The purpose of this study was to know the relation of such diseases by assessing the level of endothelin-1. Methods : SGA babies, newborns of preeclampsia and normal control mother were included in this study. Isolated endothelial cells were centrifugated and mixed with media in $37^{\circ}C$, 5% $CO_2$ to obtain confluent monolayer of cultured human umbilical venous endothelial cell (HUVEC). Endothelin-1 levels were determined by Endothelin-1 colorimetric (EIA) Kits. We examined the endothelin-1 level in the HUVEC supernatants from SGA baby, and newborns from preeclampsia as well as normal mother. Also, we compared the endothelin-1 level of cultured normal HUVEC incubated with serum from cord blood of SGA, babies of preeclampsia or normal control mother. Results : The endothelin-1 levels in cultured HUVEC supernatants of three groups showed no significant difference but the endothelin-1 levels of cultured normal HUVEC incubated with serum from preeclampsia mother or SGA mother was significantly higher than those from newborns of control mothers (P<0.05). Conclusion : These findings suggest that there may be the factor which affect the endothelin-1 level in serum of cord blood from SGA and preeclampsia.

목 적 : 본 연구자들은 전자간증, 부당 경량아, 자궁 내 발육지연 등의 질환들이 공통적으로 혈관내피세포의 기능 변화와 어느 정도 관련되어 있을 것으로 추론하였다. 따라서 전자간증 산모의 신생아, 부당 경량아의 제대혈관내피세포를 배양하여 제대의 혈관내피세포에서 발현되는 대표적인 혈관 수축작용 물질인 endothelin-1의 양을 측정한 후 정상 신생아 제대혈관 내피세포의 결과와 비교하여 각 질환에서 태아의 혈관내피세포의 endothelin-1 발현 기능에 어떤 차이가 있는지를 확인하고, 또한 배양된 정상아 제대혈관내피세포에 전자간증 산모의 신생아와 부당 경량아 및 정상아의 제대혈 혈청을 투여하여 발현된 endothelin-1의 양을 비교하여 혈청 내에 endothelin-1의 발현을 촉진시키는 인자가 있는지를 알아보았다. 방 법 : 전자간증으로 진단 받은 산모의 신생아를 전자간증군(n=7), 부당 경량아로 진단받은 신생아를 부당 경량아군(n=8), 정상 신생아를 정상군(n=12)으로 나누었다. 각 그룹에서 태어난 신생아 제대와 제대혈을 모아 제대혈은 그 혈청을 영하 $70^{\circ}C$ 이하에 보관하였다. 전자간증군, 부당 경량아군 및 정상군 신생아의 제대 혈관내피세포를 분리하고 배양하였다. 배양된 각각의 제대 혈관내피세포의 상층액에서 endothelin-1 level을 측정하였다. 다음에는 전자간증군, SGA군 및 정상군의 제대혈 혈장과 정상 신생아 제대 혈관내피세포를 함께 부양하여 그 상층액에서 endothelin-1 level을 측정하였다. 결 과 : 전자간증군, 부당 경량아군 및 정상군의 제대혈관내피세포를 배양하여 발현된 endothelin-1의 양을 측정한 결과 전자간증군과 SGA군의 제대혈관내피세포의 endothelin-1 발현은 정상군과 유의한 차이가 없었다. 그러나 배양된 정상아 제대혈관내피세포에 전자간증군과 SGA군의 제대혈 혈청을 투여하여 발현된 endothelin-1의 양은 정상군에 비하여 유의하게 증가되었다. 결 론 : 전자간증 신생아나 부당 경량아의 혈관내피세포의 기능이상을 유발하는 인자가 전자간증과 부당경량아 제대 혈청내에 존재할 가능성이 있을 것으로 생각된다.

Keywords

References

  1. Ryu KH, Choi SD, Kim HH, Lee HS, Lee JH, Kim SY, et al. The Activity of sICAM-1 and sVCAM-1 in plasma of preeclamptic mother and neonatal cord blood. J Korean Soc Neonatol 2004;11:35-43
  2. Nova A, Sibai BM, Barton JR, Mercer BM, Mitchell MD. Maternal plasma level of endothelin is increased in preeclampsia. Am J Obstet Gynecol 1991;165:724-7 https://doi.org/10.1016/0002-9378(91)90317-K
  3. Wolff K, Nisell H, Carlstrom K, Kublickiene K, Hemsen A, Lunell NO, et al. Endothelin-1 and big endothelin-1 levels in normal term pregnancy and in preeclampsia. Regul Pept 1996;67:211-6 https://doi.org/10.1016/S0167-0115(96)00122-X
  4. Roberts JM, Edep ME, Goldfien A, Taylor RN. Sera from preeclamptic women specifically activate human umbilical vein endothelial cells in vitro: morphological and biochemical evidence. Am J Reprod Immunol 1992;27:101-8 https://doi.org/10.1111/j.1600-0897.1992.tb00735.x
  5. Lee HS, Park SH, Lee WS, Kim SY, Sung IK, Chun CS. the effect of preeclampsia mother's serum and her neonatal cord blood on the activity of soluble adhesion molecules (sICAM-1) and apoptosis in Cultured human umbilical venous endothelial cells (HUVEC). J Korean Soc Neonatol 2004;11: 160-9
  6. Brazy JE, Grimm JK, Little VA. Neonatal manifestations of severe maternal hypertension occurring before the thirtysixth week of pregnancy. J Pediatr 1982;100:265-71 https://doi.org/10.1016/S0022-3476(82)80653-7
  7. Ananth CV, Peedicayil A, Savitz DA. Effect of hypertensive disease in pregnancy on birth weight, gestational duration, and small for gestational age. Epidemiology 1995;6:391-5 https://doi.org/10.1097/00001648-199507000-00011
  8. Kim SY. neonatal outcome in the hypertensive disorders of pregnancy. The Korean Journal of Perinatology 2002;13:247-53
  9. Ferrazzi E, Bulfamante G, Mezzopane R, Barbera A, Ghidini A, Pardi G. Uterine Doppler velocimetry and placental hypoxic- ischemic lesion in pregnancies with fetal intrauterine growth restriction. Placenta 1999;20:389-94 https://doi.org/10.1053/plac.1999.0395
  10. Johnson MR, Anim-Nyame N, Johnson P, Sooranna SR, Steer PJ. Does endothelial cell activation occur with intrauterine growth restriction. An International Journal of Obstetrics and Gynaecology 2002;109:836-39 https://doi.org/10.1111/j.1471-0528.2002.01045.x
  11. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM. Type 2 (non insulin dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diaetologia 1993;36:62-7 https://doi.org/10.1007/BF00399095
  12. Hales CN, Barker DJ, Clark PM, Cox LJ, Fall C, Osmond C, et al. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 1991;303:1019-22 https://doi.org/10.1136/bmj.303.6809.1019
  13. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 1989;298: 564-7 https://doi.org/10.1136/bmj.298.6673.564
  14. Barker DJ, Meade TW, Fall CH, Lee A, Osmond C, Phipps K, et al. Relation of fetal and infant growth to plasma fibrinogen and factor VII concentrations in adult life. BMJ 1992;304:148-52 https://doi.org/10.1136/bmj.304.6820.148
  15. Robinson S, Walton RJ, Clark PM, Barker DJ, Hales CN, Osmond C. The relation of fetal growth to plasma glucose in young men. Diabetologia 1992;35:444-6 https://doi.org/10.1007/BF02342441
  16. Roberts JM. Endothelial dysfunction in preeclampsia. Semin Reprod Endocrinol 1998;16:5-15 https://doi.org/10.1055/s-2007-1016248
  17. Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1986;1:1077-81
  18. Rust OA, Bofill JA, Zappe D H, Hall JE, Burnett JC, Martin JN. The origin of endothelin-1 in patients with severe preeclampsia. Obstet Gynecol 1997;89:754-7 https://doi.org/10.1016/S0029-7844(97)00093-8
  19. Yanik FF, Amanvermez R, Yanik A, Celik C, Kokcu A. Pre-eclampsia associated with increased lipid peroxidation and decreased serum vitamin E levels. Int J Gynaecol Obstet 1999;64:27-33 https://doi.org/10.1016/S0020-7292(98)00161-1
  20. Walsh SW, Wang Y. Secretion of lipid peroxides by the human placenta. Am J Obstet Gynecol 1993;169:1462-6 https://doi.org/10.1016/0002-9378(93)90419-J
  21. Hubel CA, McLaughlin MK, Evans RW, Hauth BA, Sims CJ, Roberts JM. Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum. Am J Obstet Gynecol 1996;174:975-82 https://doi.org/10.1016/S0002-9378(96)70336-8
  22. Wang YP, Walsh SW, Guo JD, Zhang JY. The imbalance between thromboxane and prostacyclin in preeclampsia is associated with an imbalance between lipid peroxides and vitamin E in maternal blood. Am J Obstet Gynecol. 1991; 165:1695-700 https://doi.org/10.1016/0002-9378(91)90017-L
  23. Sudo N, Kamoi K, Ishibashi M, Yamaji T. Plasma endothelin- 1 and big endothelin-1 levels in women with preeclampsia. Acta Endocrinol 1993;129:114-20

Cited by

  1. Streptococcus pneumoniae Serotype 19A in Children, South Korea vol.14, pp.2, 2008, https://doi.org/10.3201/eid1402.070807