Abstract
Background
Endothelial damage/dysfunction has been related to hypertension in pregnancy, with implications in pregnancy outcomes. We hypothesised abnormal levels of circulating endothelial cells (CECs), circulating progenitor cells (CPCs) and plasma von Willebrand factor (vWf, a marker of endothelial damage/dysfunction) in pregnant women with hypertension, when compared to pregnant normotensives and non pregnant healthy controls.
Methods
Our study groups were 3rd trimester hypertensive pregnant women, 40 age matched normotensive pregnant women and 50 non pregnant healthy controls. CECs were measured by immunomagnetic separation using anti-CD146 monoclonal antibody coated beads. CPCs were defined using flow cytometry as CD133+/CD34+/CD45−. vWf was measured by ELISA.
Results
Hypertensive pregnant women had significantly higher CECs compared to normotensive pregnant women and non pregnant healthy controls (p < 0.001). CPCs were raised in the normotensive pregnant group compared with hypertensive pregnant and non pregnant healthy controls (p < 0.05). Both pregnant women groups had significantly higher vWF than the non pregnant controls. CEC levels correlated with both systolic and diastolic BP (r = 0.28, p < 0.005 and r = 0.31, p < 0.001, respectively). vWf correlated with CECs (r = 0.39, p < 0.0001). Multiple linear regression analysis revealed hypertension in pregnancy as an independent predictor of CEC levels (p < 0.0001).
Conclusions
Hypertension in pregnancy is characterised by abnormalities in the vascular endothelium, with abnormal CECs and vWf that correlate with BPs. This may reflect dysfunctional processes that are counteracted with reparative attempts at restoring endothelial integrity.
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References
Karthikeyan VJ, Lip GY (2007) Hypertension in pregnancy: pathophysiology and management strategies. Curr Pharm Des 13(25):2567–2579
Germain AM, Romanik MC, Guerra I, Solari S, Reyes MS, Johnson RJ et al (2007) Endothelial dysfunction: a link among preeclampsia, recurrent pregnancy loss, and future cardiovascular events? Hypertension 49(1):90–95
George F, Brisson C, Poncelet P, Laurent JC, Massot O, Arnoux D et al (1992) Rapid isolation of human endothelial cells from whole blood using S-Endo1 monoclonal antibody coupled to immuno-magnetic beads: demonstration of endothelial injury after angioplasty. Thromb Haemost 67(1):147–153
Bardin N, Anfosso F, Masse JM, Cramer E, Sabatier F, Le Bivic A et al (2001) Identification of CD146 as a component of the endothelial junction involved in the control of cell–cell cohesion. Blood 98(13):3677–3684
Boos CJ, Lip GY, Blann AD (2006) Circulating endothelial cells in cardiovascular disease. J Am Coll Cardiol 48(8):1538–1547
Bompais H, Chagraoui J, Canron X, Crisan M, Liu XH, Anjo A et al (2004) Human endothelial cells derived from circulating progenitors display specific functional properties compared with mature vessel wall endothelial cells. Blood 103(7):2577–2584
Rafii S, Shapiro F, Rimarachin J, Nachman RL, Ferris B, Weksler B et al (1994) Isolation and characterization of human bone marrow microvascular endothelial cells: hematopoietic progenitor cell adhesion. Blood 84(1):10–19
Boyer M, Townsend LE, Vogel LM, Falk J, Reitz-Vick D, Trevor KT et al (2000) Isolation of endothelial cells and their progenitor cells from human peripheral blood. J Vasc Surg 31(1 Pt 1):181–189
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–967
Jung C, Fischer N, Fritzenwanger M, Thude H, Ferrari M, Fabris M et al (2009) Endothelial progenitor cells in adolescents: impact of overweight, age, smoking, sport and cytokines in younger age. Clin Res Cardiol 98(3):179–188
Blann AD (2006) Plasma von Willebrand factor, thrombosis, and the endothelium: the first 30 years. Thromb Haemost 95(1):49–55
Stirling Y, Woolf L, North WR, Seghatchian MJ, Meade TW (1984) Haemostasis in normal pregnancy. Thromb Haemost 52(2):176–182
Molvarec A, Rigo J Jr, Boze T, Derzsy Z, Cervenak L, Mako V et al (2009) Increased plasma von Willebrand factor antigen levels but normal von Willebrand factor cleaving protease (ADAMTS13) activity in preeclampsia. Thromb Haemost 101(2):305–311
Nadar SK, Al Yemeni E, Blann AD, Lip GY (2004) Thrombomodulin, von Willebrand factor and E-selectin as plasma markers of endothelial damage/dysfunction and activation in pregnancy induced hypertension. Thromb Res 113(2):123–128
Ogawa T, Suzuki Y, Sayama S, Soma H (1983) Possible relationship between the ratio of factor VIII complex and placental insufficiency in preeclampsia. Biol Res Pregnancy Perinatol 4(4):155–157
Canbakan B, Keven K, Tutkak H, Danisman N, Ergun I, Nergizoglu G (2007) Circulating endothelial cells in preeclampsia. J Hum Hypertens 21(7):558–563
Grundmann M, Woywodt A, Kirsch T, Hollwitz B, Oehler K, Erdbruegger U, et al. (2008) Circulating endothelial cells: a marker of vascular damage in patients with preeclampsia. Am J Obstet Gynecol 198(3):317 e1–e5
Buemi M, Allegra A, D’Anna R, Coppolino G, Crasci E, Giordano D, et al. (2007) Concentration of circulating endothelial progenitor cells (EPC) in normal pregnancy and in pregnant women with diabetes and hypertension. Am J Obstet Gynecol 196(1):68 e1–e6
Matsubara K, Abe E, Matsubara Y, Kameda K, Ito M (2006) Circulating endothelial progenitor cells during normal pregnancy and pre-eclampsia. Am J Reprod Immunol 56(2):79–85
Savvidou MD, Xiao Q, Kaihura C, Anderson JM, Nicolaides KH. (2008) Maternal circulating endothelial progenitor cells in normal singleton and twin pregnancy. Am J Obstet Gynecol 198(4):414 e1–5
Sugawara J, Mitsui-Saito M, Hayashi C, Hoshiai T, Senoo M, Chisaka H et al (2005) Decrease and senescence of endothelial progenitor cells in patients with preeclampsia. J Clin Endocrinol Metab 90(9):5329–5332
Sugawara J, Mitsui-Saito M, Hoshiai T, Hayashi C, Kimura Y, Okamura K (2005) Circulating endothelial progenitor cells during human pregnancy. J Clin Endocrinol Metab 90(3):1845–1848
Boos CJ, Lane DA, Kang D, Goon PK, Blann AD, Lip GY (2006) Temporal and venepuncture-related decline in circulating endothelial cell capture from mixed venous blood. J Thromb Thrombolysis 22(2):125–131
Woywodt A, Blann AD, Kirsch T, Erdbruegger U, Banzet N, Haubitz M et al (2006) Isolation and enumeration of circulating endothelial cells by immunomagnetic isolation: proposal of a definition and a consensus protocol. J Thromb Haemost 4(3):671–677
Woywodt A, Goldberg C, Scheer J, Regelsberger H, Haller H, Haubitz M (2004) An improved assay for enumeration of circulating endothelial cells. Ann Hematol 83(8):491–494
Goon PK, Lip GY, Stonelake PS, Blann AD (2009) Circulating endothelial cells and circulating progenitor cells in breast cancer: relationship to endothelial damage/dysfunction/apoptosis, clinicopathologic factors, and the Nottingham Prognostic Index. Neoplasia 11(8):771–779
Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H et al (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18(14):3964–3972
Evans P, Wheeler T, Anthony F, Osmond C (1997) Maternal serum vascular endothelial growth factor during early pregnancy. Clin Sci (Lond) 92(6):567–571
Leach L, Badet J, Brownbill P, Harris L, Keogh R, Kalionis B et al (2006) Endothelium, blood vessels and angiogenesis–a workshop report. Placenta 27(Suppl A):S26–S29
Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy (2000) Am J Obstet Gynecol 183(1):1–22
Hirschi KK, Ingram DA, Yoder MC (2008) Assessing identity, phenotype, and fate of endothelial progenitor cells. Arterioscler Thromb Vasc Biol 28(9):1584–1595
Acknowledgments
We acknowledge the assistance of the Sandwell and West Birmingham Hospitals NHS Trust Research & Development programme for the Haemostasis Thrombosis and Vascular Biology Unit. We also thank Mr. Balu Balakrishnan, Dr C Boos and Dr T Watson for help with laboratory work.
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Karthikeyan, V.J., Blann, A.D., Baghdadi, S. et al. Endothelial dysfunction in hypertension in pregnancy: associations between circulating endothelial cells, circulating progenitor cells and plasma von Willebrand factor. Clin Res Cardiol 100, 531–537 (2011). https://doi.org/10.1007/s00392-010-0277-9
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DOI: https://doi.org/10.1007/s00392-010-0277-9