Proteinuria is one of the hallmarks of preeclampsia (PE) that differentiates other hypertensive disorders of pregnancy. Protein misfolding and aggregation is an emerging pathological condition underlying many chronic metabolic diseases and neurodegenerative diseases. Recent studies indicate protein aggregation as an emerging biomarker of preeclampsia, wherein several proteins are aggregated and dysregulated in the body fluids of preeclamptic women, provoking the multi-systemic clinical manifestations of the disease. At the cellular level, these misfolded and aggregated proteins are potentially toxic interfering with the normal physiological process, eliciting the unfolded protein response (UPR) pathway activators in the endoplasmic reticulum (ER) that subsequently augments the ER quality control systems to remove these aberrant proteins. ER resident chaperones, folding enzymes and other proteins serve as part of the ER quality control machinery in restoring nascent protein folding. These ER chaperones are crucial for ER function aiding in native protein folding, maintaining calcium homeostasis, as sensors of ER stress and also as immune modulators. Consequently, ER chaperones seems to be involved in many cellular processes, yet the association is expanding to be explored. Understanding the role and mechanism of ER chaperones in regulating protein misfolding and aggregation would provide new avenues for therapeutic intervention as well as for the development of new diagnostic approaches.
{"title":"Cellular Functions of ER Chaperones in Regulating Protein Misfolding and Aggregation: An Emerging Therapeutic Approach for Preeclampsia","authors":"Janaranjani Murugesan, Ajithkumar Balakrishnan, Premkumar Kumpati, Hemamalini Vedagiri","doi":"10.5772/intechopen.101271","DOIUrl":"https://doi.org/10.5772/intechopen.101271","url":null,"abstract":"Proteinuria is one of the hallmarks of preeclampsia (PE) that differentiates other hypertensive disorders of pregnancy. Protein misfolding and aggregation is an emerging pathological condition underlying many chronic metabolic diseases and neurodegenerative diseases. Recent studies indicate protein aggregation as an emerging biomarker of preeclampsia, wherein several proteins are aggregated and dysregulated in the body fluids of preeclamptic women, provoking the multi-systemic clinical manifestations of the disease. At the cellular level, these misfolded and aggregated proteins are potentially toxic interfering with the normal physiological process, eliciting the unfolded protein response (UPR) pathway activators in the endoplasmic reticulum (ER) that subsequently augments the ER quality control systems to remove these aberrant proteins. ER resident chaperones, folding enzymes and other proteins serve as part of the ER quality control machinery in restoring nascent protein folding. These ER chaperones are crucial for ER function aiding in native protein folding, maintaining calcium homeostasis, as sensors of ER stress and also as immune modulators. Consequently, ER chaperones seems to be involved in many cellular processes, yet the association is expanding to be explored. Understanding the role and mechanism of ER chaperones in regulating protein misfolding and aggregation would provide new avenues for therapeutic intervention as well as for the development of new diagnostic approaches.","PeriodicalId":362368,"journal":{"name":"Preeclampsia [Working Title]","volume":"61 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121554065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-12-26DOI: 10.5772/intechopen.101240
Nissar Shaikh, S. Nahid, Firdous Ummunnisa, Ifrah Fatima, Mohamad Hilani, Asma Gul, A. Al Basha, W. Yahia, F. Al Hail, H. Elfil, E. Abdalla, M. Nainthramveetil, M.A Imraan, M. Zubair, Sibghatullah M Khan, N. Korichi, S. AlKhawaga, H. Ismail, S. Yaqoob, Mashael Abdulrahman M. S. Al Khelaifi
Preeclampsia is a hypertensive disorder of pregnancy affecting 6–12% of the population. There are various risk factors for the development of preeclampsia, ranging from advanced maternal age to genetics. The proposed etiologies for preeclampsia are abnormal placentation, immunological intolerance, endothelial damage, and genetic inheritance. The pathogenesis includes endothelial activation and dysfunction leading to vasospasm. Preeclampsia is divided into two stages: asymptomatic and symptomatic stages. Preeclampsia causes multiple organ involvement, namely central nervous system, respiratory, cardiovascular, hematological dysfunction, HELLP (hemolysis elevated liver enzymes, low platelets) syndrome, endocrine, renal, hepatic, and uteroplacental dysfunction. These organ dysfunctions increase morbidity and mortality in preeclamptic pregnant patients.
{"title":"Preeclampsia: From Etiopathology to Organ Dysfunction","authors":"Nissar Shaikh, S. Nahid, Firdous Ummunnisa, Ifrah Fatima, Mohamad Hilani, Asma Gul, A. Al Basha, W. Yahia, F. Al Hail, H. Elfil, E. Abdalla, M. Nainthramveetil, M.A Imraan, M. Zubair, Sibghatullah M Khan, N. Korichi, S. AlKhawaga, H. Ismail, S. Yaqoob, Mashael Abdulrahman M. S. Al Khelaifi","doi":"10.5772/intechopen.101240","DOIUrl":"https://doi.org/10.5772/intechopen.101240","url":null,"abstract":"Preeclampsia is a hypertensive disorder of pregnancy affecting 6–12% of the population. There are various risk factors for the development of preeclampsia, ranging from advanced maternal age to genetics. The proposed etiologies for preeclampsia are abnormal placentation, immunological intolerance, endothelial damage, and genetic inheritance. The pathogenesis includes endothelial activation and dysfunction leading to vasospasm. Preeclampsia is divided into two stages: asymptomatic and symptomatic stages. Preeclampsia causes multiple organ involvement, namely central nervous system, respiratory, cardiovascular, hematological dysfunction, HELLP (hemolysis elevated liver enzymes, low platelets) syndrome, endocrine, renal, hepatic, and uteroplacental dysfunction. These organ dysfunctions increase morbidity and mortality in preeclamptic pregnant patients.","PeriodicalId":362368,"journal":{"name":"Preeclampsia [Working Title]","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115250933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-14DOI: 10.5772/intechopen.101270
Katarina Cvitkovic, Anita Pusić Sesar, A. Sesar, I. Čavar
Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity presented with different symptoms such as visual disturbances, headaches, seizures, severe hypertension and altered mental status. It has been recognized in a different pathological conditions, although preeclampsia/eclampsia is the most common cause of PRES. The pathogenesis of PRES is still not fully understood, but it seems that failure of cerebrovascular autoregulation causing vasogenic edema, cerebral vasoconstriction, and disruption of the blood brain barrier plays an important role. Cortical blindness, hypertensive retinopathy, serous retinal detachment (SRD), central retinal artery and vein occlusions, retinal or vitreous hemorrhages, anterior ischemic optic neuropathy (AION) and Purtscher’s retinopathy are ophthalmic disorders that may occur in PRES associated with preeclampsia. Among these, cortical blindness is the best documented complication of preeclampsia. Magnet resonance imaging (MRI) is a gold standard to establish the diagnosis of PRES because clinical findings are not sufficiently specific. Typically, there are bilateral cortical occipital lesions with hyperdensity on T2-weighted MRI. Blindness due to occipital lesions is reversible and the vision loss is usually regained within 4 h to 8 days.
{"title":"Ophthalmic Disorders in Posterior Reversible Encephalopathy Syndrome Associated with Preeclampsia","authors":"Katarina Cvitkovic, Anita Pusić Sesar, A. Sesar, I. Čavar","doi":"10.5772/intechopen.101270","DOIUrl":"https://doi.org/10.5772/intechopen.101270","url":null,"abstract":"Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity presented with different symptoms such as visual disturbances, headaches, seizures, severe hypertension and altered mental status. It has been recognized in a different pathological conditions, although preeclampsia/eclampsia is the most common cause of PRES. The pathogenesis of PRES is still not fully understood, but it seems that failure of cerebrovascular autoregulation causing vasogenic edema, cerebral vasoconstriction, and disruption of the blood brain barrier plays an important role. Cortical blindness, hypertensive retinopathy, serous retinal detachment (SRD), central retinal artery and vein occlusions, retinal or vitreous hemorrhages, anterior ischemic optic neuropathy (AION) and Purtscher’s retinopathy are ophthalmic disorders that may occur in PRES associated with preeclampsia. Among these, cortical blindness is the best documented complication of preeclampsia. Magnet resonance imaging (MRI) is a gold standard to establish the diagnosis of PRES because clinical findings are not sufficiently specific. Typically, there are bilateral cortical occipital lesions with hyperdensity on T2-weighted MRI. Blindness due to occipital lesions is reversible and the vision loss is usually regained within 4 h to 8 days.","PeriodicalId":362368,"journal":{"name":"Preeclampsia [Working Title]","volume":"31 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129919387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-13DOI: 10.5772/intechopen.100337
Fred Chasalow
My laboratory discovered a new type of steroids. The structure of these steroids is unique in three ways: (i) they have 23, 24 or 25 carbon atoms – no other known vertebrate steroid has more than 21 carbon atoms; (ii) they are phosphodiesters – no other steroid phosphodiesters are known; and (iii) some of them have a spiral steroid at carbon 17 – no other endogenous spiral steroids are known. In total, our laboratory had elucidated the structure and path of biosynthesis for more than 20 related compounds. We have developed an LC–MS method and a MS–MS method to measure the compounds in small samples (< 1 ml). Synthetic compounds with similar spiral steroids (e.g., spironolactone) function as potassium sparing hormones but there were no known endogenous hormones with this function. We propose that the natural spiral steroids have that function. Endogenous compounds with these functions would have important roles in the physiology of pregnancy, pre-eclampsia, and eclampsia. This chapter will review the proposed physiology and pathology of the spiral steroids during pregnancy. There are many details to confirm but this is a useful paradigm.
{"title":"Role of Spiral Steroids in Pregnancy and Pre-Eclampsia","authors":"Fred Chasalow","doi":"10.5772/intechopen.100337","DOIUrl":"https://doi.org/10.5772/intechopen.100337","url":null,"abstract":"My laboratory discovered a new type of steroids. The structure of these steroids is unique in three ways: (i) they have 23, 24 or 25 carbon atoms – no other known vertebrate steroid has more than 21 carbon atoms; (ii) they are phosphodiesters – no other steroid phosphodiesters are known; and (iii) some of them have a spiral steroid at carbon 17 – no other endogenous spiral steroids are known. In total, our laboratory had elucidated the structure and path of biosynthesis for more than 20 related compounds. We have developed an LC–MS method and a MS–MS method to measure the compounds in small samples (< 1 ml). Synthetic compounds with similar spiral steroids (e.g., spironolactone) function as potassium sparing hormones but there were no known endogenous hormones with this function. We propose that the natural spiral steroids have that function. Endogenous compounds with these functions would have important roles in the physiology of pregnancy, pre-eclampsia, and eclampsia. This chapter will review the proposed physiology and pathology of the spiral steroids during pregnancy. There are many details to confirm but this is a useful paradigm.","PeriodicalId":362368,"journal":{"name":"Preeclampsia [Working Title]","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126603895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-03DOI: 10.5772/intechopen.100139
S. Kharb
Pathogenesis of preeclampsia involves immune dysfunction, placental implantation, abnormal angiogenesis, excessive inflammation, hypertension that may be affected by vitamin D. Human placenta expresses all the components for vitamin D signaling: Vitamin D receptor (VDR), retinoid X receptor (RXR), 1-alpha- hydroxylase (CYP27B1) and 24- hydroxylase (CYP24A1). Vitamin D binding protein plays a role in binding and transportation of 25 hydroxyvitamin D [25(OH)D] and 1,25(OH)2D3. Vitamin D is activated by 25-hydroxylase (CYP2R1) and 1-alpha -hydroxylase (CYP27B1) and is degraded by 24-hydroxylase (CYP24A1). Vitamin D supplementation is not recommended by WHO for pregnant women and allows recommended nutrient intake (RNI) of 200 IU (5 μg) per day. Further research requires serum 25(OH)D analysis and assessment of maternal and infant outcomes; pre-conceptional vitamin D status.
{"title":"Role of Vitamin D in Preeclampsia","authors":"S. Kharb","doi":"10.5772/intechopen.100139","DOIUrl":"https://doi.org/10.5772/intechopen.100139","url":null,"abstract":"Pathogenesis of preeclampsia involves immune dysfunction, placental implantation, abnormal angiogenesis, excessive inflammation, hypertension that may be affected by vitamin D. Human placenta expresses all the components for vitamin D signaling: Vitamin D receptor (VDR), retinoid X receptor (RXR), 1-alpha- hydroxylase (CYP27B1) and 24- hydroxylase (CYP24A1). Vitamin D binding protein plays a role in binding and transportation of 25 hydroxyvitamin D [25(OH)D] and 1,25(OH)2D3. Vitamin D is activated by 25-hydroxylase (CYP2R1) and 1-alpha -hydroxylase (CYP27B1) and is degraded by 24-hydroxylase (CYP24A1). Vitamin D supplementation is not recommended by WHO for pregnant women and allows recommended nutrient intake (RNI) of 200 IU (5 μg) per day. Further research requires serum 25(OH)D analysis and assessment of maternal and infant outcomes; pre-conceptional vitamin D status.","PeriodicalId":362368,"journal":{"name":"Preeclampsia [Working Title]","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131627620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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