Abstract
Purpose
To identify whether CGRP and PTHrP serve as screening biomarkers for early detection of preeclampsia or even before the development of preeclampsia in early pregnancy.
Methods
It was a nested case–control study. The subjects were divided into normotensive (controls) and preeclamptic (cases) groups. Serum samples of 132 cases and 132 controls were collected during pregnancy at three different gestational periods and one sample post delivery, from within the cohort of pregnant women reporting to antenatal clinic. Circulating levels of CGRP and PTHrP were analyzed by enzyme-linked immunosorbent assay.
Results
Maternal serum concentrations of CGRP and PTHrP increased with the advancement of gestation age in both normotensive and preeclamptic pregnancies but the significantly less increased levels were observed in preeclamptic pregnancies as compared with normotensive pregnancies. In postpartum period level of CGRP significantly falls in both groups although level of PTHrP continues to increase even after delivery. Maternal serum CGRP and PTHrP concentrations were positively correlated with the infant’s birth weights.
Conclusion
Maternal circulating CGRP and PTHrP concentrations were significantly lower in women with preeclampsia, which may contribute to the development of preeclampsia.
References
Duvekott JJ, Cheriex EC, Pieters FAA et al (1993) Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adjustments triggered by a fall in systemic vascular tone. Am J Obstet Gynecol 169:1382–1392
Robertson WB, Brosens I, Dixon HG (1967) The pathological response of the vessels of the placental bed to hypertensive pregnancy. J Pathol Bacteriol 93:581–592
Gerretsen G, Huisjes HJ, Elema JD (1981) Morphological changes of the spiral arteries in the placental bed in relation to pre-eclampsia and fetal growth retardation. Br J Obstet Gynaecol 88:876–881
World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy (1988) Geographic variation in the incidence of hypertension in pregnancy. Am J Obst Gynecol 158:80–83
WHO (2005) Make every mother and child count, in the world health report 2005. World Health Organization, Geneva
Osungbade OK, Ige OK (2011) Public heath perspectives of preeclampsia in developing countries: implication for health system strengthening. J Pregnancy 2011:481095. doi:10.1155/2011/481095
Williams D (2011) Long-term complications of pre-eclampsia. Semin Nephrol 31(1):111–122
Young BC, Levine RJ, Karumanchi SA (2010) Pathogenesis of preeclampsia. Annu Rev Pathol 5:173–192
Baviera G, D’Anna R, Corrado F, Ruello A, Buemi M, Jasonni VM (2002) ICAM-1 in maternal plasma and amniotic fluid as an early marker of pre-eclampsia and IUGR. J Reprod Med 47(3):191–193
Bell D, McDermott BJ (1996) Calcitonin gene-related peptide in the cardio-vascular system: characterization of receptor populations and their pathophysiological significance. Pharmacol Rev 48:253–288
Wimalawansa SJ (1996) Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials. Endocr Rev 17:533–585
DiPette DJ, Wimalawansa SJ (1995) Calcium regulating hormones and cardio-vascular function. In: Cross JI, Aveoli LV (eds) Cardiovascular actions of calcitropic hormones. CRC, Baltimore, pp 239–252
Asimakis GK, DiPette DJ, Conti VR, Holland OB, Zwischenberger JB (1987) Hemodynamic action of calcitonin gene-related peptide in the isolated rat heart. Life Sci 41:597–603
Yallampalli C, Dong YL, Wimalawansa SJ (1996) Calcitonin gene-related peptide reverses the hypertension and significantly decreases the fetal mortality in preeclampsia rats induced by NG-nitro-l-arginine methyl ester. Hum Reprod 11(4):895–899
Gude NM, King RG, Brennecke SP (1996) Factors regulating placenta hemodynamics. In: Sastry BVR (ed) Placental pharmacology. CRC, Boca Raton, pp 23–45
Maggi CA, Meli A (1988) The sensor-efferent function of capsaicin-sensitive neurons. Gen Pharmacol 19(1):1–43
Roberts JM (2000) Preeclampsia: what we know and what we do not know. Semin Perinatol 24:24–28
Brosens JJ, Pijnenborg R, Brosens IA (2002) The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: a review of the literature. Am J Obstet Gynecol 187:1416–1423
Robertson WB, Brosens I, Dixon G (1976) Maternal uterine vascular lesions in the hypertensive complications of pregnancy. Perspect Nephrol Hypertens 5:115–127
Zhou Y, Fisher SJ, Janatpour M et al (1997) Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion? J Clin Invest 99:2139–2151
Roberts JM (1998) Endothelial dysfunction in preeclampsia. Semin Reprod Endocrinol 16:5–15
Levine RJ, Maynard SE, Qian C et al (2004) Circulating angiogenic factors and the risk of pre-eclampsia. N Engl J Med 350:672–683
Fisher SJ, Roberts JM (1999) Defects in placentation and placental perfusion. In: Lindheimer MD, Roberts JM, Cunningham FG (eds) Chelsey’s hypertensive disorders in pregnancy, 2nd edn. Appleton and Lange, pp 377–394
Rinehart BK et al (1999) Expression of the placental cytokines tumor necrosis factor alpha, interleukin 1beta, and interleukin 10 is increased in preeclampsia. Am J Obstet Gynecol 181:915–920
Roberts JM, Taylor RN, Goldfien A (1991) Clinical and biochemical evidence of endothelial cell dysfunction in the pregnancy syndrome preeclampsia. Am J Hypertens 4:700–708
Chen Yu (2009) Novel angiogenic factors for predicting preeclampsia: sFlt-1, PlGF, and soluble endoglin. Open Clin Chem J 2:1–6
Seely EW, Wood RJ, Brown EM, Graves SW (1992) Lower serum ionized calcium and abnormal calciotropic hormone levels in preeclampsia. J Clin Endocrinol Metab 74:1436–1440
Halhali A, Tovar AR, Torres N, Bourges H, Garabe´dian M, Larrea F (2000) Preeclampsia is associated with low circulating levels of insulin like growth factor I and 1,25-dihydroxyvitamin D in maternal and umbilical cord compartments. J Clin Endocrinol Metab 85:1828–1833
Wimalawansa SJ (1993) Antihypertensive effects of oral calcium supplementation is mediated through the potent vasodilator CGRP. Am J Hypertens 6:996–1002
Wimalawansa SJ, Supowit SC, DiPette DJ (1995) Mechanisms of the antihypertensive effects of dietary calcium and role of calcitonin gene-related peptide in hypertension. Can J Physiol Pharmacol 73:981–985
Wysolmerski JJ, Stewart AF (1998) The physiology of parathyroid hormone-related protein: an emerging role as a developmental factor. Annu Rev Physiol 60:431–460
Ariza AC, Bobadilla N, Diaz L, Avila E, Larrea F, Halhali A (2009) Placental gene expression of calcitonin gene related peptide and nitric oxide synthases in preeclampsia: effects of magnesium sulfate. Magnes Res 22(1):44–49
Halhali A, Wimalawansa SJ, Berentsen V, Avila E, Thota CS, Larrea F (2001) Calcitonin gene and parathyroid hormone related peptides in preeclampsia: effects of magnesium sulfate. Obstet Gynecol 97(6):893–897
Gangula PR, Zhao H, Wimalawansa SJ, Supowit SC, DiPette DJ, Yallampalli C (2001) Pregnancy and steroid hormones enhance the systemic and regional hemodynamic effects of calcitonin gene-related peptide in rats. Biol Reprod 64(6):1776–1783
Stevenson JC, Macdonald DW, Warren RC, Booker MW, Whitehead MI (1986) Increased concentration of circulating calcitonin gene related peptide during normal human pregnancy. Br Med J 293(6558):1329–1330
Taquet H, Uzan S (1992) Plasma calcitonin gene-related peptide during gestation (Letter). Lancet 340:1170
Thota C, Gangula PR, Dong YL, Yallampalli C (2003) Changes in the expression of calcitonin receptor-like receptor, receptor activity-modifying protein (RAMP) 1, RAMP2, and RAMP3 in rat uterus during pregnancy, labor, and by steroid hormone treatments. Biol Reprod 69(4):1432–1437
Dong YL, Vegiraju S, Gangula PR, Kondapaka SB, Wimalawansa SJ, Yallampalli C (2002) Expression and regulation of calcitonin gene-related peptide receptor in rat placentas. Biol Reprod 67(4):1321–1326
Gallacher SJ, Fraser WD, Owens OJ et al (1994) Changes in calciotrophic hormones and biochemical markers of bone turnover in normal human pregnancy. Eur J Endocrinol 131:369–374
Ardawi MS, Nasrat HA, BA’Aqueel HS (1997) Calcium regulating hormones and parathyroid hormone-related peptide in normal human pregnancy and postpartum: a longitudinal study. Eur J Endocrinol 137:402–409
Lippuner K, Zehnder HJ, Casez JP, Takkinen R, Jaeger P (1996) PTH-related protein is released into the mother’s bloodstream during location: evidence for beneficial effects on maternal calcium-phosphate metabolism. J Bone Miner Res 11(10):1394–1399
Sowers MF, Hollis BW, Shapiro B, Randolph J, Janney CA, Zhang D (1996) Elevated parathyroid hormone-related peptide associated with lactation and bone density loss. JAMA 276(7):549–554
Dobnig H, Kainer F, Stepan V et al (1995) Elevated parathyroid hormone-related peptide levels after human gestation: relationship to changes in bone and mineral metabolism. J Clin Endocrinol Metab 80:3699–3707
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We are grateful to Uttar Pradesh Council of Science and Technology (UPCST) for the financial support.
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Yadav, S., Yadav, Y.S., Goel, M.M. et al. Calcitonin gene- and parathyroid hormone-related peptides in normotensive and preeclamptic pregnancies: a nested case–control study. Arch Gynecol Obstet 290, 897–903 (2014). https://doi.org/10.1007/s00404-014-3303-8
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DOI: https://doi.org/10.1007/s00404-014-3303-8