Reduced Number of Endothelial Progenitor Colony-Forming Units in Patients with Preeclampsia

  • Kim, Shin-Young (Laboratory of Medical Genetics, Cheil General Hospital and Women's Healthcare Center) ;
  • Park, So-Yeon (Laboratory of Medical Genetics, Cheil General Hospital and Women's Healthcare Center) ;
  • Kim, Jin-Woo (Laboratory of Medical Genetics, Cheil General Hospital and Women's Healthcare Center) ;
  • Lee, Mi-Bum (Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine) ;
  • Han, You-Jung (Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine) ;
  • Ahn, Hyun-Kyong (Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine) ;
  • Choi, Jun-Seek (Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine) ;
  • Han, Jung-Yeol (Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine) ;
  • Kim, Moon-Young (Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine) ;
  • Choi, Kyu-Hong (Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine) ;
  • Ryu, Hyun-Mee (Laboratory of Medical Genetics, Cheil General Hospital and Women's Healthcare Center)
  • Received : 2010.11.04
  • Accepted : 2010.12.24
  • Published : 2010.12.01

Abstract

Purpose: Endothelial progenitor cells (EPCs), which mediates neovascularization of uterine endometrium may be involved in the neovascularization in the utero-placental circulation. Low numbers of endothelial progenitor colony-forming unit (CFU) in culture are predictive biomarker of vascular disease. The aim of the present study was to evaluate whether the number of CFU in preeclampsia differed from that in normal pregnancy. Materials and Methods: Women with singleton normal (n=26) or preeclamptic (n=20) pregnancies were studied during the third trimester. The number of EPCs was quantified by CFU methodology. Plasma levels of angiogenic factors, vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and placental growth factor (PlGF) were determined by enzyme-linked immunoassay. Results: CFU numbers were significantly decreased in the preeclamptic patients compared with the controls (median, 3; range 1-12 vs. 31; 3-81 CFU/well, P<0.001). A majority of the cells comprising individual colonies were positive for endothelial characteristics (Ulex europaeus lectin staining and acetylated low-density lipoprotein uptake). Plasma levels of the sFlt-1 were highly elevated (P<0.001) in patient with preeclampsia compared to controls, whereas PlGF were highly reduced (P=0.004), but these factors did not associate with CFU numbers. Conclusion: Our results suggest that reduced numbers of CFU obtained from maternal peripheral blood may contribute to the development of preeclampsia.

목 적: 자궁내막의 신혈관 형성을 조정하는 혈관내피전구세포는 자궁-태반 순환에서의 신혈관 형성에 관여하는 것으로 알려져 있다. 혈관내피전구세포의 정량적 지표로 사용되는 집락생성단위(CFU)의 감소는 혈관질환의 예측 표지자로서 보고되고 있다. 본 연구에서는 정상 산모와 자간전증 산모 간에 CFU의 수적인 차이를 비교해 보고자 하였다. 대상 및 방법: 임신말기의 단태 정상 산모 26명과 자간전증산모 20명을 대상으로 혈관내피전구세포의 수를 CFU로 정량화하였다. 효소면역분석법을 이용하여 혈장내의 VEGF와 sFlt-1, PlGF 농도를 분석하였다. 결 과: CFU의 수는 정상 산모에 비해 자간전증 산모에서 매우 감소하였다[median value: 3 (range: 1-12) vs median value: 31(range:3-81) CFU/ well, P<0.001). 집락을 구성하는 대부분의 세포는 혈관내피세포의 특징적인 성질을 보였다(Ulex europaeus lectin의 발현 및 acetylated lowdensity lipoprotein의 섭취). 혈장내의 sFlt-1 농도는 정상 산모에 비해 자간전증 산모에서 매우 높은 반면(P<0.001), PlGF의 농도는 매우 낮았으며(P=0.004), sFlt-1과 PlGF의 농도는 CFU의 수와 연관성이 없었다. 결 론: 산모 말초혈액내의 CFU의 수적 감소가 자간전증 발생에 기여할 것으로 생각된다.

Keywords

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