Angiotensin II and angiotensin-(1-7) decrease sFlt1 release in normal but not preeclamptic chorionic villi: an in vitro study
Tóm tắt
During preeclampsia, placental angiogenesis is impaired. Factors released from the placenta including vascular endothelial growth factor (VEGF), placental growth factor (PLGF), soluble VEGF receptor 1 (sFlt1), and soluble endoglin (sEng) are regulatory molecules of placental development and function. While the renin angiotensin system has been shown to regulate angiogenic factors in other research fields, these mechanisms have not been extensively studied during pregnancy. We evaluated the effects of angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)] on the release of VEGF, PLGF, sFlt1, and sEng from placental chorionic villi (CV). CV were collected from nulliparous third-trimester normotensive and preeclamptic subjects. CV were incubated for 0, 2, 4, and 16 hours with or without Ang II (1 nM and 1 microM) or Ang-(1-7) (1 nM and 1 microM). The release of VEGF, PLGF, sFlt1, sEng, lactate dehydrogenase (LDH), and human placenta lactogen (HPL) was measured by ELISA. The release of sFlt1, PLGF, sEng from normal and preeclamptic CV increased over time. Release of sFlt1 and sEng was significantly higher from preeclamptic CV. VEGF was below the detectable level of the assay in normal and preeclamptic CV. After 2 hours, sFlt1 release from normal CV was significantly inhibited with Ang II (1 nM and 1 microM) and Ang-(1-7) (1 nM and 1 microM). There was a time-dependent increase in HPL indicating that the CV were functioning normally. Our study demonstrates a critical inhibitory role of angiotensin peptides on sFlt1 in normal pregnancy. Loss of this regulation in preeclampsia may allow sFlt1 to increase resulting in anti-angiogenesis and end organ damage in the mother.
Tài liệu tham khảo
The Working Group on High Blood Pressure in Pregnancy. National High Blood Pressure Education Program (NHPEP): Working group report on high blood pressure in pregnancy. US Dept. Health and Human Services. 1991, 91-3029. 1-46
Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z: Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999, 13: 9-22.
Petrova TV, Makinen T, Alitalo K: Signaling via vascular endothelial growth factor receptors. Exp Cell Res. 1999, 253: 117-130. 10.1006/excr.1999.4707.
Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Epstein FH, Sukhatme VP, Karumanchi SA: Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003, 111: 649-658.
Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, Bdolah Y, Lim KH, Yuan HT, Libermann TA, Stillman IE, Roberts D, D'Amore PA, Epstein FH, Sellke FW, Romero R, Sukhatme VP, Letarte M, Karumanchi SA: Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006, 12: 642-649. 10.1038/nm1429.
Fisher SJ, Roberts JM: Defects in placentation and placental perfusion. Chesley's Disorders in Pregnancy. Edited by: Lindheimer M, Roberts JM, Cunningham FG. 1999, Stanford: Appleton & Lange, 377-394. 2
Granger JP, Alexander BT, Llinas MT, Bennett WA, Khalil RA: Pathophysiology of preeclampsia: linking placental ischemia/hypoxia with microvascular dysfunction. Microcirculation. 2002, 9: 147-160.
Taylor RN, Roberts JM: Endothelial cell dysfunction. Chesley's Hypertensive Disorders in Pregnancy. Edited by: Lindheimer M, Roberts JM, Cunningham FG. 1999, Stanford: Appleton & Lange, 395-429. 2
Kendall RL, Thomas KA: Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci USA. 1993, 90: 10705-10709. 10.1073/pnas.90.22.10705.
Cheifetz S, Bellon T, Cales C, Vera S, Bernabeu C, Massague J, Letarte M: Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem. 1992, 267: 19027-19030.
Gougos A, St Jacques S, Greaves A, O'Connell PJ, d'Apice AJ, Buhring HJ, Bernabeu C, van Mourik JA, Letarte M: Identification of distinct epitopes of endoglin, an RGD-containing glycoprotein of endothelial cells, leukemic cells, and syncytiotrophoblasts. Int Immunol. 1992, 4: 83-92. 10.1093/intimm/4.1.83.
St-Jacques S, Forte M, Lye SJ, Letarte M: Localization of endoglin, a transforming growth factor-beta binding protein, and of CD44 and integrins in placenta during the first trimester of pregnancy. Biol Reprod. 1994, 51: 405-413. 10.1095/biolreprod51.3.405.
Nasjletti A, Masson GMC: Studies on angiotensinogen formation in a liver perfusion system. Circ Res [Suppl II]. 1972, 30: 187-202.
Tewksbury DA: Angiotensinogen -- Biochemistry and Molecular Biology. Hypertension: Pathophysiology, Diagnosis and Management. Edited by: Laragh JH, Brenner BM. 1990, New York: Raven Press, 1197-1216.
Chen Y, Naftilan AJ, Oparil S: Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats. Hypertension. 1992, 19: 456-463.
Rubattu S, Quimby FW, Sealey JE: Tissue renin and prorenin increase in female cats during the reproductive cycle without commensurate changes in plasma, amniotic or ovarian follicular fluid. J Hypertens. 1991, 9: 525-535. 10.1097/00004872-199106000-00008.
Glorioso N, Atlas SA, Laragh JH, Jewelewicz R, Sealey JE: Prorenin in high concentrations in human ovarian follicular fluid. Science. 1986, 233: 1422-1424. 10.1126/science.3529392.
Howard RB, Pucell AG, Bumpus FM, Husain A: Rat ovarian renin: Characterization and changes during the estrous cycle. Endocrinology. 1988, 123: 2331-2340. 10.1210/endo-123-5-2331.
Brosnihan KB, Santos RAS, Block CH, Schiavone MT, Welches WR, Chappell MC, Khosla MC, Greene LJ, Ferrario CM: Biotransformation of angiotensins in the central nervous system. Ther Res. 1988, 9: 48-59.
Ferrario CM, Chappell MC: A new myocardial conversion of angiotensin I. Curr Opin Cardiol. 1994, 9: 520-526. 10.1097/00001573-199409000-00004.
Merrill DC, Karoly M, Chen K, Ferrario CM, Brosnihan KB: Angiotensin-(1-7) in normal and preeclamptic pregnancy. Endocrine. 2002, 18: 239-245. 10.1385/ENDO:18:3:239.
Valdes G, Germain AM, Corthorn J, Berrios C, Foradori AC, Ferrario CM, Brosnihan KB: Urinary vasodilator and vasoconstrictor angiotensins during menstrual cycle, pregnancy, and lactation. Endocrine. 2001, 16: 117-122. 10.1385/ENDO:16:2:117.
Anton L, Merrill DC, Neves LAA, Stovall K, Gallagher PE, Diz DI, Moorefield C, Gruver C, Ferrario CM, Brosnihan KB: Activation of local chorionic villi angiotensin II levels but not angiotensin (1-7) in preeclampsia. Hypertension. 2008, 51: 1066-1072. 10.1161/HYPERTENSIONAHA.107.103861.
Williams B: A potential role for angiotensin II-induced vascular endothelial growth factor expression in the pathogenesis of diabetic nephropathy. Miner Electrolyte Metab. 1998, 24: 400-405. 10.1159/000057401.
Otani A, Takagi H, Suzuma K, Honda Y: Angiotensin II potentiates vascular endothelial growth factor--induced angiogenic activity in retinal microcapillary endothelial cells. Circ Res. 1998, 82: 619-628.
Chua CC, Hamdy RC, Chua BH: Upregulation of vascular endothelial growth factor by angiotensin II in rat heart endothelial cells. Biochim Biophys Acta. 1998, 1401: 187-194. 10.1016/S0167-4889(97)00129-8.
Fujiyama S, Matsubara H, Nozawa Y, Maruyama K, Mori Y, Tsutsumi Y, Masaki H, Uchiyama Y, Koyama Y, Nose A, Iba O, Tateishi E, Ogata N, Jyo N, Higashiyama S, Iwasaka T: Angiotensin AT(1) and AT(2) receptors differentially regulate angiopoietin-2 and vascular endothelial growth factor expression and angiogenesis by modulating heparin binding-epidermal growth factor (EGF)-mediated EGF receptor transactivation. Circ Res. 2001, 88: 22-29.
Amaral SL, Linderman JR, Morse MM, Greene AS: Angiogenesis induced by electrical stimulation is mediated by angiotensin II and VEGF. Microcirculation. 2001, 8: 57-67.
Ahmad S, Ahmed A: Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia. Circ Res. 2004, 95: 884-891. 10.1161/01.RES.0000147365.86159.f5.
Soothill PW, Nicolaides KH, Rodeck CH, Campbell S: Effect of gestational age on fetal and intervillous blood gas and acid-base values in human pregnancy. Fetal Ther. 1986, 1: 168-175. 10.1159/000262264.
Fujikura T, Yoshida J: Blood gas analysis of placental and uterine blood during cesarean delivery. Obstet Gynecol. 1996, 87: 133-136. 10.1016/0029-7844(95)00300-2.
Zhou CC, Ahmad S, Mi T, Xia L, Abbasi S, Hewett PW, Sun C, Ahmed A, Kellems RE, Xia Y: Angiotensin II induces soluble fms-like tyrosine kinase-1 release via calcineurin signaling pathway in pregnancy. Circ Res. 2007, 100: 88-95. 10.1161/01.RES.0000254703.11154.18.
Anton L, Merrill DC, Neves LA, Brosnihan KB: Angiotensin-(1-7) inhibits in vitro endothelial cell tube formation in human umbilical vein endothelial cells through the AT(1-7) receptor. Endocrine. 2007, 32: 212-218. 10.1007/s12020-007-9022-1.
Machado RD, Santos RA, Andrade SP: Mechanisms of angiotensin-(1-7)-induced inhibition of angiogenesis. American Journal of Physiology - Regulatory Integrative & Comparative Physiology. 2001, 280: R994-R1000.
Machado RD, Santos RA, Andrade SP: Opposing actions of angiotensins on angiogenesis. Life Sci. 2000, 66: 67-76. 10.1016/S0024-3205(99)00562-7.
Menon J, Soto-Pantoja DR, Callahan MF, Cline JM, Ferrario CM, Tallant EA, Gallagher PE: Angiotensin-(1-7) inhibits growth of human lung adenocarcinoma xenografts in nude mice through a reduction in cyclooxygenase-2. Cancer Res. 2007, 67: 2809-2815. 10.1158/0008-5472.CAN-06-3614.
Schiavone MT, Santos RAS, Brosnihan KB, Khosla MC, Ferrario CM: Release of vasopressin from the rat hypothalamo-neurohypophysial system by angiotensin-(1-7) heptapeptide. Proc Natl Acad Sci USA. 1988, 85: 4095-4098. 10.1073/pnas.85.11.4095.
Rowe BP, Saylor DL, Speth RC, Absher DR: Angiotensin-(1-7) binding at angiotensin II receptors in the rat brain. Regul Pept. 1995, 56: 139-146. 10.1016/0167-0115(95)00010-9.
Tallant EA, Lu X, Weiss RB, Chappell MC, Ferrario CM: Bovine aortic endothelial cells contain an angiotensin-(1-7) receptor. Hypertension. 1997, 29: 388-392.
Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA: Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004, 350: 672-683. 10.1056/NEJMoa031884.
Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, De MM, Wu Y, Bono F, Devy L, Beck H, Scholz D, Acker T, DiPalma T, Dewerchin M, Noel A, Stalmans I, Barra A, Blacher S, Vandendriessche T, Ponten A, Eriksson U, Plate KH, Foidart JM, Schaper W, Charnock-Jones DS, Hicklin DJ, Herbert JM, Collen D, Persico MG: Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 2001, 7: 575-583. 10.1038/87904.
Taylor RN, Grimwood J, Taylor RS, McMaster MT, Fisher SJ, North RA: Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies. Am J Obstet Gynecol. 2003, 188: 177-182. 10.1067/mob.2003.111.