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Role of statin as inducer of Hmox-1 system in treatment of preeclampsia
Corresponding Author(s) : Ridwan A Putra
Cellular and Molecular Biology,
Vol. 64 No. 10: Issue 10
Abstract
Preeclampsia is the major cause of both maternal and neonatal morbidity and mortality. Its insidence remains high and the management has not been established yet because its etiology and pathophysiological are still poorly understood. Theories regarding etiopathogenesis and management of preeclampsia have been postulated yet it remains controversial. Placental ischemic and angiogenic imbalance are suggested to be predisposing factors of preeclampsia. It is thereby targeted in prevention of preeclampsia. Unfortunately, both primary and secondary prevention using various supplements and drugs fails to exhibit good outcome. Overall, these efforts are considered useless. In recent years, researchers have been using statin derivative in management of preclampsia. It has been reported that statin provides protective effect in endothelial cells by inducing expression of Hmox-1 and inihibiting release of sFlt-1 as well as potent antioxidant properties. Thus, statin has been proposed as promising agent to significantly reduce anti-angiogenic in preeclamptic patients which is overviewed in this review based on recent studies.
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- Cheng CL, Agoestina T, Harbin J. Maternal mortality at twelve teaching hospital in Indonesia. Int J Gynecol Obstet 2005;19:260-7.
- Ahmed A. New insights into the etiology of preeclampsia: identification of key exclusive factors for the vascular complications. Thromb Res 2011;127:S72-5.
- Ramma W, Ahmed A. Is inflammation the cause of pre-eclampsia? Biochem Soc Trans 2011;39:1619-27.
- Redman CWG Sargent IL. Latest Advances in Understanding Preeclampsia. Science 2005;308:1592-4
- Fatima N, Islam F, Noor L, Das SR, Zeba D, Zesmin F. Serum ferritin in preeclampsia and eclampsia: a case control study. Faridpur Med Coll 2013;8:18-21.
- Siddiqui IA, Jaleel A, Kadri HM, Saeed WA, Tamimi W. Iron status parameters in preeclamptic women. Arch Gynecol Obstet 2011;284:587-91.
- Mutter WP, Karumanchi SA. Molecular mechanism of preeclamsia. Microvasc Res. 2008;75:1-8.
- Lam C, Lim KH, Karumanchi SA. Circulating angiogenic factor in the pathogenesis and prediction of preeclampsia. Hypertension 2005: 46: 1077-85.
- Dvorak HF. Vascular permeability factor/vasculer endhotelial growth factor: A critical cytokine in tumor angiogenesis and a potential target for diagnosid and therapy. J. Clin Oncol 2002;20;4368-80.
- Lindheimer MD, Romero R. Emerging roles of antiangiogenic proteins in pathogenesis and prediction of preeclampsia. Hypertension 2007;50:35-6.
- Walther M, Caul AD, Aka P, Njie M, Amambua-Ngwa A, Walther B, et al. Hmox1 gene promoter alleles and high HO-1 levels are associated with severe malaria in Gambian Children. Plos Pathog 2012;8:1-17.
- Ahmed A, Cudmore MJ. Can the biology of VEGF and haemoxygenases help solve pre-eclampsia? Biochem Soc Trans 2009;37:1237-44.
- Cudmore M, Ahmad S, Al-Ani B, Fujisawa T, Coxall H, Chudasama K, et al. Negative Regulation of Soluble Flt-1 and Soluble Endoglin Release by Heme Oxygenase-1. Circulation. 2007;115:1789-97.
- Putra RA, Effendi JE. Sabarudin U. Korelasi Kadar Ferritrin serum dengan heme oksigenase-1 (Hmox-1) pada penderita preeklamsi dan hamil normal. Divisi Kedokteran Fetomaternal Bagian Obsetri dan Ginekologi. FK UNPAD/RSHS Bandung. 2015:1-94.
- Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database of Systematic Reviews. 2007(1).
- Conde-Agudelo A, Romero R, Kusanovic JP, Hassan SS. Suplementation with vitamins C and E during pregnancy for the prevention of preeclampsia and other adverse maternal and perinatal outcomes: a systematic review and metaanalysis. Am J Obstet Gynecol 2011;204(6):503.e1-.e12.
- Ramma W, Ahmed A. Therapeutic potential of statins and the induction of heme oxygenase-1 in preeclampsia. J Reprod Immunol 2014;29(4101-102):153-60.
- Ahmed A, Rahman M, Zhang X, Avecedo CH, Nijjar S, Rushton I, et al. Induction of placental heme oxygenase-1 is protective against TNFalpha-induced cytotoxicity and pomotes vessel relaxation. Mol Med 2000;6:391-409.
- Fox KA, Longo M, Tamayo E, Kechichian T, Bytautiene E, Hankins GDV, et al. Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1–induced preeclampsia. Am J Obstet Gynecol. 2011;205:366.e1-.e5.
- Cao J, Inoue K, Li X, Drummond G, Abraham NG. Physiological significance of heme oxygenase-1 in hypertension. Int J Biochem Cell Biol 2009;41:1025-33.
- Wikstrom AK, Stephansson O, Chattingius S. Tobacco use during pregnancy and preeclampsia risk: effects of cigarette smoking and snuff. Hypertension 2010;55:1254-9.
- Vera T, Kelsen S, Stec DE. Kidney-specific induction of heme oxygenase-1 prevents angiotensin II hypertension. Hypertension 2008;52:660-5.
- Ahmed A, Williams D. Statins to Ameliorate early onset Preeclampsia : a proof of principle, double-blind, randomised placebocontrolled, multicentre trial of pravastatin to ameliorate early onset pre-eclampsia. 2009.
- Ofori B, Rey E, Bérard A. Risk of congenital anomalies in pregnant users of statin drugs. British J Clinic Pharmacol 2007;64:496-509.
- Petersen EE, Mitchell AA, Carey JC, Werler MM, Louik C, Rasmussen SA. Maternal exposure to statins and risk for birth defects: A case-series approach. Am J Med Genet Part A 2008;146A:2701-5.
- Winterfeld U, Allignol A, Panchaud A, Rothuizen LE, Merlob P, Cuppers-Maarschalkerweerd B, et al. Pregnancy outcome following maternal exposure to statins: a multicentre prospective study. BJOG: An Int J Obstet Gynaecol 2013;120:463-71.
References
Cheng CL, Agoestina T, Harbin J. Maternal mortality at twelve teaching hospital in Indonesia. Int J Gynecol Obstet 2005;19:260-7.
Ahmed A. New insights into the etiology of preeclampsia: identification of key exclusive factors for the vascular complications. Thromb Res 2011;127:S72-5.
Ramma W, Ahmed A. Is inflammation the cause of pre-eclampsia? Biochem Soc Trans 2011;39:1619-27.
Redman CWG Sargent IL. Latest Advances in Understanding Preeclampsia. Science 2005;308:1592-4
Fatima N, Islam F, Noor L, Das SR, Zeba D, Zesmin F. Serum ferritin in preeclampsia and eclampsia: a case control study. Faridpur Med Coll 2013;8:18-21.
Siddiqui IA, Jaleel A, Kadri HM, Saeed WA, Tamimi W. Iron status parameters in preeclamptic women. Arch Gynecol Obstet 2011;284:587-91.
Mutter WP, Karumanchi SA. Molecular mechanism of preeclamsia. Microvasc Res. 2008;75:1-8.
Lam C, Lim KH, Karumanchi SA. Circulating angiogenic factor in the pathogenesis and prediction of preeclampsia. Hypertension 2005: 46: 1077-85.
Dvorak HF. Vascular permeability factor/vasculer endhotelial growth factor: A critical cytokine in tumor angiogenesis and a potential target for diagnosid and therapy. J. Clin Oncol 2002;20;4368-80.
Lindheimer MD, Romero R. Emerging roles of antiangiogenic proteins in pathogenesis and prediction of preeclampsia. Hypertension 2007;50:35-6.
Walther M, Caul AD, Aka P, Njie M, Amambua-Ngwa A, Walther B, et al. Hmox1 gene promoter alleles and high HO-1 levels are associated with severe malaria in Gambian Children. Plos Pathog 2012;8:1-17.
Ahmed A, Cudmore MJ. Can the biology of VEGF and haemoxygenases help solve pre-eclampsia? Biochem Soc Trans 2009;37:1237-44.
Cudmore M, Ahmad S, Al-Ani B, Fujisawa T, Coxall H, Chudasama K, et al. Negative Regulation of Soluble Flt-1 and Soluble Endoglin Release by Heme Oxygenase-1. Circulation. 2007;115:1789-97.
Putra RA, Effendi JE. Sabarudin U. Korelasi Kadar Ferritrin serum dengan heme oksigenase-1 (Hmox-1) pada penderita preeklamsi dan hamil normal. Divisi Kedokteran Fetomaternal Bagian Obsetri dan Ginekologi. FK UNPAD/RSHS Bandung. 2015:1-94.
Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database of Systematic Reviews. 2007(1).
Conde-Agudelo A, Romero R, Kusanovic JP, Hassan SS. Suplementation with vitamins C and E during pregnancy for the prevention of preeclampsia and other adverse maternal and perinatal outcomes: a systematic review and metaanalysis. Am J Obstet Gynecol 2011;204(6):503.e1-.e12.
Ramma W, Ahmed A. Therapeutic potential of statins and the induction of heme oxygenase-1 in preeclampsia. J Reprod Immunol 2014;29(4101-102):153-60.
Ahmed A, Rahman M, Zhang X, Avecedo CH, Nijjar S, Rushton I, et al. Induction of placental heme oxygenase-1 is protective against TNFalpha-induced cytotoxicity and pomotes vessel relaxation. Mol Med 2000;6:391-409.
Fox KA, Longo M, Tamayo E, Kechichian T, Bytautiene E, Hankins GDV, et al. Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1–induced preeclampsia. Am J Obstet Gynecol. 2011;205:366.e1-.e5.
Cao J, Inoue K, Li X, Drummond G, Abraham NG. Physiological significance of heme oxygenase-1 in hypertension. Int J Biochem Cell Biol 2009;41:1025-33.
Wikstrom AK, Stephansson O, Chattingius S. Tobacco use during pregnancy and preeclampsia risk: effects of cigarette smoking and snuff. Hypertension 2010;55:1254-9.
Vera T, Kelsen S, Stec DE. Kidney-specific induction of heme oxygenase-1 prevents angiotensin II hypertension. Hypertension 2008;52:660-5.
Ahmed A, Williams D. Statins to Ameliorate early onset Preeclampsia : a proof of principle, double-blind, randomised placebocontrolled, multicentre trial of pravastatin to ameliorate early onset pre-eclampsia. 2009.
Ofori B, Rey E, Bérard A. Risk of congenital anomalies in pregnant users of statin drugs. British J Clinic Pharmacol 2007;64:496-509.
Petersen EE, Mitchell AA, Carey JC, Werler MM, Louik C, Rasmussen SA. Maternal exposure to statins and risk for birth defects: A case-series approach. Am J Med Genet Part A 2008;146A:2701-5.
Winterfeld U, Allignol A, Panchaud A, Rothuizen LE, Merlob P, Cuppers-Maarschalkerweerd B, et al. Pregnancy outcome following maternal exposure to statins: a multicentre prospective study. BJOG: An Int J Obstet Gynaecol 2013;120:463-71.