Generic placeholder image

Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Review Article

Inflammasomes in the Pathophysiology of Maternal Obesity: Potential Therapeutic Targets to Reduce Long-Term Adverse Health Outcomes in the Mother and Offspring

Author(s): Padma Murthi* and Gayathri Rajaraman

Volume 19, Issue 2, 2021

Published on: 03 June, 2020

Page: [165 - 175] Pages: 11

DOI: 10.2174/1570161118666200603131536

Price: $65

Abstract

Over the past 20 years, the prevalence of obesity has risen dramatically worldwide, with an increase in occurrence among women in their reproductive age. Obesity during pregnancy is associated with significantly increased maternal and fetal morbidity and mortality. In addition to the short-term adverse health outcomes, both mother and the child are prone to develop cardiovascular, metabolic and neurological disorders. Although associations between obesity during pregnancy and adverse maternalfetal health outcomes are clear, the complex molecular mechanisms underlying maternal obesity remain largely unknown. This review describes multimeric self-assembling protein complexes, namely inflammasomes, as potential molecular targets in the pathophysiology of maternal obesity. Inflammasomes are implicated in both normal physiological and in pathophysiological processes that occur in response to an inflammatory milieu throughout gestation. This review highlights the current knowledge of inflammasome expression and its activity in pregnancies affected by maternal obesity. Key discussions in defining pharmacological inhibition of upstream as well as downstream targets of the inflammasome signaling cascade; and the inflammasome platform, as a potential therapeutic strategy in attenuating the pathophysiology underpinning inflammatory component in maternal obesity are presented herein.

Keywords: Maternal obesity, pregnancy, placenta, inflammation, inflammasomes, maternal care.

Graphical Abstract
[1]
Flegal KM, Kruszon-Moran D, Carroll MD, Fryar CD, Ogden CL. Trends in obesity among adults in the United States, 2005 to 2014. JAMA 2016; 315(21): 2284-91.
[http://dx.doi.org/10.1001/jama.2016.6458] [PMID: 27272580]
[2]
Poston L, Caleyachetty R, Cnattingius S, et al. Preconceptional and maternal obesity: epidemiology and health consequences. Lancet Diabetes Endocrinol 2016; 4(12): 1025-36.
[http://dx.doi.org/10.1016/S2213-8587(16)30217-0] [PMID: 27743975]
[3]
Gaillard R, Durmuş B, Hofman A, Mackenbach JP, Steegers EA, Jaddoe VW. Risk factors and outcomes of maternal obesity and excessive weight gain during pregnancy. Obesity (Silver Spring) 2013; 21(5): 1046-55.
[http://dx.doi.org/10.1002/oby.20088] [PMID: 23784909]
[4]
Cnattingius S, Villamor E, Johansson S, et al. Maternal obesity and risk of preterm delivery. JAMA 2013; 309(22): 2362-70.
[http://dx.doi.org/10.1001/jama.2013.6295] [PMID: 23757084]
[5]
Metzger BE, Lowe LP, Dyer AR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358(19): 1991-2002.
[http://dx.doi.org/10.1056/NEJMoa0707943] [PMID: 18463375]
[6]
Gaudet L, Ferraro ZM, Wen SW, Walker M. Maternal obesity and occurrence of fetal macrosomia: a systematic review and meta-analysis. BioMed Res Int 2014; 2014640291
[http://dx.doi.org/10.1155/2014/640291] [PMID: 25544943]
[7]
Çınar M, Timur H, Aksoy RT, et al. Evaluation of maternal and perinatal outcomes among overweight women who experienced stillbirth. J Matern Fetal Neonatal Med 2017; 30(1): 38-42.
[http://dx.doi.org/10.3109/14767058.2016.1152255] [PMID: 26857830]
[8]
Wang J, Moore D, Subramanian A, et al. Gestational dyslipidaemia and adverse birthweight outcomes: a systematic review and meta-analysis. Obes Rev 2018; 19(9): 1256-68.
[http://dx.doi.org/10.1111/obr.12693] [PMID: 29786159]
[9]
Suk D, Kwak T, Khawar N, et al. Increasing maternal body mass index during pregnancy increases neonatal intensive care unit admission in near and full-term infants. J Matern Fetal Neonatal Med 2016; 29(20): 3249-53.
[http://dx.doi.org/10.3109/14767058.2015.1124082] [PMID: 26601691]
[10]
Faucett AM, Metz TD, DeWitt PE, et al. Effect of obesity on neonatal outcomes in pregnancies with preterm premature rupture of membranes. Am J Obstet Gynecol 2016; 214(2): 287.
[http://dx.doi.org/10.1016/j.ajog.2015.09.093]
[11]
McGillick EV, Lock MC, Orgeig S, Morrison JL. Maternal obesity mediated predisposition to respiratory complications at birth and in later life: understanding the implications of the obesogenic intrauterine environment. Paediatr Respir Rev 2017; 21: 11-8.
[PMID: 27818069]
[12]
Mina TH, Lahti M, Drake AJ, et al. Prenatal exposure to maternal very severe obesity is associated with impaired neurodevelopment and executive functioning in children. Pediatr Res 2017; 82(1): 47-54.
[http://dx.doi.org/10.1038/pr.2017.43] [PMID: 28288149]
[13]
Stacy SL, Buchanich JM, Ma ZQ, et al. Maternal obesity, birth size, and risk of childhood cancer development. Am J Epidemiol 2019; 188(8): 1503-11.
[http://dx.doi.org/10.1093/aje/kwz118] [PMID: 31107539]
[14]
Tran LT, Lai HTM, Koriyama C, Uwatoko F, Akiba S. The association between high birth weight and the risks of childhood CNS tumors and leukemia: an analysis of a US case-control study in an epidemiological database. BMC Cancer 2017; 17(1): 687.
[http://dx.doi.org/10.1186/s12885-017-3681-y] [PMID: 29037176]
[15]
Edlow AG. Maternal obesity and neurodevelopmental and psychiatric disorders in offspring. Prenat Diagn 2017; 37(1): 95-110.
[http://dx.doi.org/10.1002/pd.4932] [PMID: 27684946]
[16]
Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH. Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med 1997; 337(13): 869-73.
[http://dx.doi.org/10.1056/NEJM199709253371301] [PMID: 9302300]
[17]
Gaillard R, Steegers EA, Duijts L, et al. Childhood cardiometabolic outcomes of maternal obesity during pregnancy: the Generation R Study. Hypertension 2014; 63(4): 683-91.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.02671] [PMID: 24379180]
[18]
Catalano PM, Presley L, Minium J, Hauguel-de Mouzon S. Fetuses of obese mothers develop insulin resistance in utero. Diabetes Care 2009; 32(6): 1076-80.
[http://dx.doi.org/10.2337/dc08-2077] [PMID: 19460915]
[19]
Jones CW. Gestational diabetes and its impact on the neonate. Neonatal Netw 2001; 20(6): 17-23.
[http://dx.doi.org/10.1891/0730-0832.20.6.17] [PMID: 12144115]
[20]
Kalagiri RR, Carder T, Choudhury S, et al. Inflammation in complicated pregnancy and its outcome. Am J Perinatol 2016; 33(14): 1337-56.
[http://dx.doi.org/10.1055/s-0036-1582397] [PMID: 27159203]
[21]
Myatt L, Maloyan A. Obesity and placental function. Semin Reprod Med 2016; 34(1): 42-9.
[http://dx.doi.org/10.1055/s-0035-1570027] [PMID: 26734917]
[22]
Stewart FM, Freeman DJ, Ramsay JE, Greer IA, Caslake M, Ferrell WR. Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers. J Clin Endocrinol Metab 2007; 92(3): 969-75.
[http://dx.doi.org/10.1210/jc.2006-2083] [PMID: 17192290]
[23]
Pantham P, Aye IL, Powell TL. Inflammation in maternal obesity and gestational diabetes mellitus. Placenta 2015; 36(7): 709-15.
[http://dx.doi.org/10.1016/j.placenta.2015.04.006] [PMID: 25972077]
[24]
Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006; 444(7121): 860-7.
[http://dx.doi.org/10.1038/nature05485] [PMID: 17167474]
[25]
Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011; 29: 415-45.
[http://dx.doi.org/10.1146/annurev-immunol-031210-101322] [PMID: 21219177]
[26]
Catalano PM, Huston L, Amini SB, Kalhan SC. Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am J Obstet Gynecol 1999; 180(4): 903-16.
[http://dx.doi.org/10.1016/S0002-9378(99)70662-9] [PMID: 10203659]
[27]
Chen X, Scholl TO. Association of elevated free fatty acids during late pregnancy with preterm delivery. Obstet Gynecol 2008; 112(2 Pt 1): 297-303.
[http://dx.doi.org/10.1097/AOG.0b013e3181802150] [PMID: 18669726]
[28]
Boden G. Interaction between free fatty acids and glucose metabolism. Curr Opin Clin Nutr Metab Care 2002; 5(5): 545-9.
[http://dx.doi.org/10.1097/00075197-200209000-00014] [PMID: 12172479]
[29]
Wen H, Gris D, Lei Y, et al. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol 2011; 12(5): 408-15.
[http://dx.doi.org/10.1038/ni.2022] [PMID: 21478880]
[30]
Christian LM, Porter K. Longitudinal changes in serum proinflammatory markers across pregnancy and postpartum: effects of maternal body mass index. Cytokine 2014; 70(2): 134-40.
[http://dx.doi.org/10.1016/j.cyto.2014.06.018] [PMID: 25082648]
[31]
Aye IL, Lager S, Ramirez VI, et al. Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways. Biol Reprod 2014; 90(6): 129.
[http://dx.doi.org/10.1095/biolreprod.113.116186] [PMID: 24759787]
[32]
Basu S, Haghiac M, Surace P, et al. Pregravid obesity associates with increased maternal endotoxemia and metabolic inflammation. Obesity (Silver Spring) 2011; 19(3): 476-82.
[http://dx.doi.org/10.1038/oby.2010.215] [PMID: 20930711]
[33]
Challier JC, Basu S, Bintein T, et al. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 2008; 29(3): 274-81.
[http://dx.doi.org/10.1016/j.placenta.2007.12.010] [PMID: 18262644]
[34]
Hauguel-de Mouzon S, Guerre-Millo M. The placenta cytokine network and inflammatory signals. Placenta 2006; 27(8): 794-8.
[http://dx.doi.org/10.1016/j.placenta.2005.08.009] [PMID: 16242770]
[35]
Roberts KA, Riley SC, Reynolds RM, et al. Placental structure and inflammation in pregnancies associated with obesity. Placenta 2011; 32(3): 247-54.
[http://dx.doi.org/10.1016/j.placenta.2010.12.023] [PMID: 21232790]
[36]
Saben J, Lindsey F, Zhong Y, et al. Maternal obesity is associated with a lipotoxic placental environment. Placenta 2014; 35(3): 171-7.
[http://dx.doi.org/10.1016/j.placenta.2014.01.003] [PMID: 24484739]
[37]
McMillen IC, Robinson JS. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 2005; 85(2): 571-633.
[http://dx.doi.org/10.1152/physrev.00053.2003] [PMID: 15788706]
[38]
Fowden AL, Forhead AJ, Coan PM, Burton GJ. The placenta and intrauterine programming. J Neuroendocrinol 2008; 20(4): 439-50.
[http://dx.doi.org/10.1111/j.1365-2826.2008.01663.x] [PMID: 18266944]
[39]
Myatt L. Placental adaptive responses and fetal programming. J Physiol 2006; 572(Pt 1): 25-30.
[http://dx.doi.org/10.1113/jphysiol.2006.104968] [PMID: 16469781]
[40]
Jansson T, Powell TL. Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches. Clin Sci (Lond) 2007; 113(1): 1-13.
[http://dx.doi.org/10.1042/CS20060339] [PMID: 17536998]
[41]
Higgins L, Mills TA, Greenwood SL, Cowley EJ, Sibley CP, Jones RL. Maternal obesity and its effect on placental cell turnover. J Matern Fetal Neonatal Med 2013; 26(8): 783-8.
[http://dx.doi.org/10.3109/14767058.2012.760539] [PMID: 23270521]
[42]
Jansson N, Rosario FJ, Gaccioli F, et al. Activation of placental mTOR signaling and amino acid transporters in obese women giving birth to large babies. J Clin Endocrinol Metab 2013; 98(1): 105-13.
[http://dx.doi.org/10.1210/jc.2012-2667] [PMID: 23150676]
[43]
Mele J, Muralimanoharan S, Maloyan A, Myatt L. Impaired mitochondrial function in human placenta with increased maternal adiposity. Am J Physiol Endocrinol Metab 2014; 307(5): E419-25.
[http://dx.doi.org/10.1152/ajpendo.00025.2014] [PMID: 25028397]
[44]
DuBois BN, O’Tierney-Ginn P, Pearson J, Friedman JE, Thornburg K, Cherala G. Maternal obesity alters feto-placental cytochrome P4501A1 activity. Placenta 2012; 33(12): 1045-51.
[http://dx.doi.org/10.1016/j.placenta.2012.09.008] [PMID: 23046808]
[45]
Hayward CE, Higgins L, Cowley EJ, et al. Chorionic plate arterial function is altered in maternal obesity. Placenta 2013; 34(3): 281-7.
[http://dx.doi.org/10.1016/j.placenta.2013.01.001] [PMID: 23360794]
[46]
Aye IL, Jansson T, Powell TL. Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts. Mol Cell Endocrinol 2013; 381(1-2): 46-55.
[http://dx.doi.org/10.1016/j.mce.2013.07.013] [PMID: 23891856]
[47]
Saben J, Zhong Y, Gomez-Acevedo H, et al. Early growth response protein-1 mediates lipotoxicity-associated placental inflammation: role in maternal obesity. Am J Physiol Endocrinol Metab 2013; 305(1): E1-E14.
[http://dx.doi.org/10.1152/ajpendo.00076.2013] [PMID: 23632636]
[48]
Laskewitz A, van Benthem KL, Kieffer TEC, et al. The influence of maternal obesity on macrophage subsets in the human decidua. Cell Immunol 2019; 336: 75-82.
[http://dx.doi.org/10.1016/j.cellimm.2019.01.002] [PMID: 30665661]
[49]
Mor G, Cardenas I, Abrahams V, Guller S. Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci 2011; 1221: 80-7.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05938.x] [PMID: 21401634]
[50]
Jansson N, Greenwood SL, Johansson BR, Powell TL, Jansson T. Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments. J Clin Endocrinol Metab 2003; 88(3): 1205-11.
[http://dx.doi.org/10.1210/jc.2002-021332] [PMID: 12629107]
[51]
Jones HN, Jansson T, Powell TL. IL-6 stimulates system A amino acid transporter activity in trophoblast cells through STAT3 and in-creased expression of SNAT2. Am J Physiol Cell Physiol 2009; 297(5): C1228-35.
[http://dx.doi.org/10.1152/ajpcell.00195.2009] [PMID: 19741197]
[52]
Lager S, Jansson N, Olsson AL, Wennergren M, Jansson T, Powell TL. Effect of IL-6 and TNF-α on fatty acid uptake in cultured human primary trophoblast cells. Placenta 2011; 32(2): 121-7.
[http://dx.doi.org/10.1016/j.placenta.2010.10.012] [PMID: 21144584]
[53]
Place DE, Kanneganti TD. Recent advances in inflammasome biology. Curr Opin Immunol 2018; 50: 32-8.
[http://dx.doi.org/10.1016/j.coi.2017.10.011] [PMID: 29128729]
[54]
Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol 2016; 16(7): 407-20.
[http://dx.doi.org/10.1038/nri.2016.58] [PMID: 27291964]
[55]
Tschopp J, Martinon F, Burns K. NALPs: a novel protein family involved in inflammation. Nat Rev Mol Cell Biol 2003; 4(2): 95-104.
[http://dx.doi.org/10.1038/nrm1019] [PMID: 12563287]
[56]
Khan RN, Hay DP. A clear and present danger: inflammasomes DAMPing down disorders of pregnancy. Hum Reprod Update 2015; 21(3): 388-405.
[http://dx.doi.org/10.1093/humupd/dmu059] [PMID: 25403436]
[57]
I.CW M, Romao Veiga, M.L. Matias, et al. Increased expression of NLRP3 inflammasome in placentas from pregnant women with severe preeclampsia. J Reprod Immunol 2017; 123: 40-7.
[58]
Kesavardhana S, Kanneganti TD. Mechanisms governing inflammasome activation, assembly and pyroptosis induction. Int Immunol 2017; 29(5): 201-10.
[http://dx.doi.org/10.1093/intimm/dxx018] [PMID: 28531279]
[59]
Kayagaki N, Stowe IB, Lee BL, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 2015; 526(7575): 666-71.
[http://dx.doi.org/10.1038/nature15541] [PMID: 26375259]
[60]
Franchi L, Eigenbrod T, Muñoz-Planillo R, Nuñez G. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol 2009; 10(3): 241-7.
[http://dx.doi.org/10.1038/ni.1703] [PMID: 19221555]
[61]
Ilekis JV, Tsilou E, Fisher S, et al. Placental origins of adverse pregnancy outcomes: potential molecular targets: an executive workshop summary of the eunice kennedy shriver national institute of child health and human development. Am J Obstet Gynecol 2016; 215(Suppl. 1): 1-46.
[http://dx.doi.org/10.1016/j.ajog.2016.03.001] [PMID: 26972897]
[62]
Mariathasan S, Newton K, Monack DM, et al. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 2004; 430(6996): 213-8.
[http://dx.doi.org/10.1038/nature02664] [PMID: 15190255]
[63]
Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 2002; 10(2): 417-26.
[http://dx.doi.org/10.1016/S1097-2765(02)00599-3] [PMID: 12191486]
[64]
Zhong FL, Mamai O, Sborgi L, et al. Germline NLRP1 mutations cause skin inflammatory and cancer susceptibility syndromes via in-flammasome activation. Cell 2016; 167(1): 187-202.
[http://dx.doi.org/10.1016/j.cell.2016.09.001]
[65]
Poyet JL, Srinivasula SM, Tnani M, Razmara M, Fernandes-Alnemri T, Alnemri ES. Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1. J Biol Chem 2001; 276(30): 28309-13.
[http://dx.doi.org/10.1074/jbc.C100250200] [PMID: 11390368]
[66]
Grenier JM, Wang L, Manji GA, et al. Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1. FEBS Lett 2002; 530(1-3): 73-8.
[http://dx.doi.org/10.1016/S0014-5793(02)03416-6] [PMID: 12387869]
[67]
Khare S, Dorfleutner A, Bryan NB, et al. An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages. Immunity 2012; 36(3): 464-76.
[http://dx.doi.org/10.1016/j.immuni.2012.02.001] [PMID: 22361007]
[68]
Wang L, Manji GA, Grenier JM, et al. PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing. J Biol Chem 2002; 277(33): 29874-80.
[http://dx.doi.org/10.1074/jbc.M203915200] [PMID: 12019269]
[69]
Pothlichet J, Meunier I, Davis BK, et al. Type I IFN triggers RIG-I/TLR3/NLRP3-dependent inflammasome activation in influenza A virus infected cells. PLoS Pathog 2013; 9(4)e1003256
[http://dx.doi.org/10.1371/journal.ppat.1003256] [PMID: 23592984]
[70]
Monroe KM, Yang Z, Johnson JR, et al. IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV. Science 2014; 343(6169): 428-32.
[http://dx.doi.org/10.1126/science.1243640] [PMID: 24356113]
[71]
Orsi NM, Tribe RM. Cytokine networks and the regulation of uterine function in pregnancy and parturition. J Neuroendocrinol 2008; 20(4): 462-9.
[http://dx.doi.org/10.1111/j.1365-2826.2008.01668.x] [PMID: 18266939]
[72]
Evans J, Salamonsen LA, Winship A, et al. Fertile ground: human endometrial programming and lessons in health and disease. Nat Rev Endocrinol 2016; 12(11): 654-67.
[http://dx.doi.org/10.1038/nrendo.2016.116] [PMID: 27448058]
[73]
Romero R, Espinoza J, Gonçalves LF, Kusanovic JP, Friel LA, Nien JK. Inflammation in preterm and term labour and delivery. Semin Fetal Neonatal Med 2006; 11(5): 317-26.
[http://dx.doi.org/10.1016/j.siny.2006.05.001] [PMID: 16839830]
[74]
Yin Y, Yan Y, Jiang X, et al. Inflammasomes are differentially expressed in cardiovascular and other tissues. Int J Immunopathol Pharmacol 2009; 22(2): 311-22.
[http://dx.doi.org/10.1177/039463200902200208] [PMID: 19505385]
[75]
Pontillo A, Girardelli M, Agostinis C, Masat E, Bulla R, Crovella S. Bacterial LPS differently modulates inflammasome gene expression and IL-1β secretion in trophoblast cells, decidual stromal cells, and decidual endothelial cells. Reprod Sci 2013; 20(5): 563-6.
[http://dx.doi.org/10.1177/1933719112459240] [PMID: 23184659]
[76]
Tilburgs T, Meissner TB, Ferreira LMR, et al. NLRP2 is a suppressor of NF-ƙB signaling and HLA-C expression in human trophoblasts. Biol Reprod 2017; 96(4): 831-42.
[http://dx.doi.org/10.1093/biolre/iox009] [PMID: 28340094]
[77]
Bryant AH, Bevan RJ, Spencer-Harty S, Scott LM, Jones RH, Thornton CA. Expression and function of NOD-like receptors by human term gestation-associated tissues. Placenta 2017; 58: 25-32.
[http://dx.doi.org/10.1016/j.placenta.2017.07.017] [PMID: 28962692]
[78]
Gomez-Lopez N, Romero R, Panaitescu B, et al. Inflammasome activation during spontaneous preterm labor with intra-amniotic infection or sterile intra-amniotic inflammation. Am J Reprod Immunol 2018; 80(5)e13049
[http://dx.doi.org/10.1111/aji.13049] [PMID: 30225853]
[79]
Panaitescu B, Romero R, Gomez-Lopez N, et al. In vivo evidence of inflammasome activation during spontaneous labor at term. J Matern Fetal Neonatal Med 2019; 32(12): 1978-91.
[http://dx.doi.org/10.1080/14767058.2017.1422714] [PMID: 29295667]
[80]
Romero R, Xu Y, Plazyo O, et al. A Role for the Inflammasome in Spontaneous Labor at Term. Am J Reprod Immunol 2018; 79(6)e12440
[http://dx.doi.org/10.1111/aji.12440] [PMID: 26952361]
[81]
Gomez-Lopez N, Motomura K, Miller D, Garcia-Flores V, Galaz J, Romero R. Inflammasomes: their role in normal and complicated pregnancies. J Immunol 2019; 203(11): 2757-69.
[http://dx.doi.org/10.4049/jimmunol.1900901] [PMID: 31740550]
[82]
Gomez-Lopez N, Romero R, Xu Y, et al. Inflammasome assembly in the chorioamniotic membranes during spontaneous labor at term. Am J Reprod Immunol 2017; 77(5): 10.
[http://dx.doi.org/10.1111/aji.12648] [PMID: 28233423]
[83]
Kohli S, Isermann B. Placental hemostasis and sterile inflammation: New insights into gestational vascular disease. Thromb Res 2017; 151(Suppl. 1): S30-3.
[http://dx.doi.org/10.1016/S0049-3848(17)30063-4] [PMID: 28262230]
[84]
Mulla MJ, Myrtolli K, Potter J, et al. Uric acid induces trophoblast IL-1β production via the inflammasome: implications for the pathogenesis of preeclampsia. Am J Reprod Immunol 2011; 65(6): 542-8.
[http://dx.doi.org/10.1111/j.1600-0897.2010.00960.x] [PMID: 21352397]
[85]
Stødle GS, Silva GB, Tangerås LH, et al. Placental inflammation in pre-eclampsia by Nod-like receptor protein (NLRP)3 inflammasome activation in trophoblasts. Clin Exp Immunol 2018; 193(1): 84-94.
[http://dx.doi.org/10.1111/cei.13130] [PMID: 29683202]
[86]
Aye ILMH, Lager S, Powell TL. The role of placental inflammasomes in linking the adverse effects of maternal obesity on fetal development.In: Metabolic syndrome and complications of pregnancy: the potential role of nutrition. Springer 2015; pp. 77-90.
[http://dx.doi.org/10.1007/978-3-319-16853-1_6]
[87]
Aye ILMH, Ramirez VI, Gaccioli F, Lager S, Jansson T, Powell TL. Activation of placental inflammasomes in pregnant women with high BMI. Reprod Sci 2013; 20(S3): 73A.
[88]
Kavathas PB, Boeras CM, Mulla MJ, Abrahams VM. Nod1, but not the ASC inflammasome, contributes to induction of IL-1β secretion in human trophoblasts after sensing of Chlamydia trachomatis. Mucosal Immunol 2013; 6(2): 235-43.
[http://dx.doi.org/10.1038/mi.2012.63] [PMID: 22763410]
[89]
Abi Nahed R, Reynaud D, Borg AJ, et al. NLRP7 is increased in human idiopathic fetal growth restriction and plays a critical role in trophoblast differentiation. J Mol Med (Berl) 2019; 97(3): 355-67.
[http://dx.doi.org/10.1007/s00109-018-01737-x] [PMID: 30617930]
[90]
Zhao J, Zheng DY, Yang JM, et al. Maternal serum uric acid concentration is associated with the expression of tumour necrosis factor-α and intercellular adhesion molecule-1 in patients with preeclampsia. J Hum Hypertens 2016; 30(7): 456-62.
[http://dx.doi.org/10.1038/jhh.2015.110] [PMID: 26511169]
[91]
Matias ML, Romão M, Weel IC, et al. Endogenous and uric acid-induced activation of NLRP3 inflammasome in pregnant women with preeclampsia. PLoS One 2015; 10(6)e0129095
[http://dx.doi.org/10.1371/journal.pone.0129095] [PMID: 26053021]
[92]
Krishnan SM, Dowling JK, Ling YH, et al. Inflammasome activity is essential for one kidney/deoxycorticosterone acetate/salt-induced hypertension in mice. Br J Pharmacol 2016; 173(4): 752-65.
[http://dx.doi.org/10.1111/bph.13230] [PMID: 26103560]
[93]
Zhou L, Xiao X. The role of gut microbiota in the effects of maternal obesity during pregnancy on offspring metabolism. Biosci Rep 2018; 38(2)BSR20171234
[http://dx.doi.org/10.1042/BSR20171234] [PMID: 29208770]
[94]
Vinayagam D, Leslie K, Khalil A, Thilaganathan B. Preeclampsia - What is to blame? The placenta, maternal cardiovascular system or both? World J Obstet Gynecol 2015; 4(4): 77-85.
[http://dx.doi.org/10.5317/wjog.v4.i4.77]
[95]
Mokkala K, Röytiö H, Munukka E, et al. Gut microbiota richness and composition and dietary intake of overweight pregnant women are related to serum zonulin concentration, a marker for intestinal permeability. J Nutr 2016; 146(9): 1694-700.
[http://dx.doi.org/10.3945/jn.116.235358] [PMID: 27466607]
[96]
Vinaik R, Barayan D, Abdullahi A, Jeschke MG. NLRP3 inflammasome mediates white adipose tissue browning after burn. Am J Physiol Endocrinol Metab 2019; 317(5): E751-9.
[http://dx.doi.org/10.1152/ajpendo.00180.2019] [PMID: 31453709]
[97]
Strakova Z, Srisuparp S, Fazleabas AT. Interleukin-1beta induces the expression of insulin-like growth factor binding protein-1 during decidualization in the primate. Endocrinology 2000; 141(12): 4664-70.
[http://dx.doi.org/10.1210/endo.141.12.7810] [PMID: 11108281]
[98]
Fortunato SJ, Menon R. IL-1 beta is a better inducer of apoptosis in human fetal membranes than IL-6. Placenta 2003; 24(10): 922-8.
[http://dx.doi.org/10.1016/S0143-4004(03)00160-7] [PMID: 14580374]
[99]
Keelan JA, Groome NP, Mitchell MD. Regulation of activin-A production by human amnion, decidua and placenta in vitro by pro-inflammatory cytokines. Placenta 1998; 19(5-6): 429-34.
[http://dx.doi.org/10.1016/S0143-4004(98)90084-4] [PMID: 9699965]
[100]
Tsukihara S, Harada T, Deura I, et al. Interleukin-1beta-induced expression of IL-6 and production of human chorionic gonadotropin in human trophoblast cells via nuclear factor-kappaB activation. Am J Reprod Immunol 2004; 52(3): 218-23.
[http://dx.doi.org/10.1111/j.1600-0897.2004.00209.x] [PMID: 15373762]
[101]
Seki H, Zosmer A, Elder MG, Sullivan MH. The regulation of progesterone and hCG production from placental cells by interleukin-1beta. Biochim Biophys Acta 1997; 1336(2): 342-8.
[http://dx.doi.org/10.1016/S0304-4165(97)00042-1] [PMID: 9305807]
[102]
Pasqua T, Pagliaro P, Rocca C, Angelone T, Penna C. Role of NLRP-3 inflammasome in hypertension: a potential therapeutic target. Curr Pharm Biotechnol 2018; 19(9): 708-14.
[http://dx.doi.org/10.2174/1389201019666180808162011] [PMID: 30091406]
[103]
Cavalera M, Wang J, Frangogiannis NG. Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological pathways, molecular mechanisms, and therapeutic opportunities. Transl Res 2014; 164(4): 323-35.
[http://dx.doi.org/10.1016/j.trsl.2014.05.001] [PMID: 24880146]
[104]
Liu P, Xie Q, Wei T, Chen Y, Chen H, Shen W. Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats. Biochem Biophys Res Commun 2015; 468(1-2): 319-25.
[http://dx.doi.org/10.1016/j.bbrc.2015.10.105] [PMID: 26514727]
[105]
Kai H, Kuwahara F, Tokuda K, Imaizumi T. Diastolic dysfunction in hypertensive hearts: roles of perivascular inflammation and reactive myocardial fibrosis. Hypertens Res 2005; 28(6): 483-90.
[http://dx.doi.org/10.1291/hypres.28.483] [PMID: 16231753]
[106]
Manabe I, Shindo T, Nagai R. Gene expression in fibroblasts and fibrosis: involvement in cardiac hypertrophy. Circ Res 2002; 91(12): 1103-13.
[http://dx.doi.org/10.1161/01.RES.0000046452.67724.B8] [PMID: 12480810]
[107]
Pardo A, Selman M. Matrix metalloproteases in aberrant fibrotic tissue remodeling. Proc Am Thorac Soc 2006; 3(4): 383-8.
[http://dx.doi.org/10.1513/pats.200601-012TK] [PMID: 16738205]
[108]
Chen CP, Aplin JD. Placental extracellular matrix: gene expression, deposition by placental fibroblasts and the effect of oxygen. Placenta 2003; 24(4): 316-25.
[http://dx.doi.org/10.1053/plac.2002.0904] [PMID: 12657504]
[109]
Li W, Cui N, Mazzuca MQ, Mata KM, Khalil RA. Increased vascular and uteroplacental matrix metalloproteinase-1 and -7 levels and collagen type I deposition in hypertension in pregnancy: role of TNF-α. Am J Physiol Heart Circ Physiol 2017; 313(3): H491-507.
[http://dx.doi.org/10.1152/ajpheart.00207.2017] [PMID: 28626073]
[110]
LaMarca B, Speed J, Fournier L, et al. Hypertension in response to chronic reductions in uterine perfusion in pregnant rats: effect of tumor necrosis factor-alpha blockade. Hypertension 2008; 52(6): 1161-7.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.120881] [PMID: 18981324]
[111]
LaMarca BB, Bennett WA, Alexander BT, Cockrell K, Granger JP. Hypertension produced by reductions in uterine perfusion in the pregnant rat: role of tumor necrosis factor-alpha. Hypertension 2005; 46(4): 1022-5.
[http://dx.doi.org/10.1161/01.HYP.0000175476.26719.36] [PMID: 16144982]
[112]
Chen J, Khalil RA. Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia. Prog Mol Biol Transl Sci 2017; 148: 87-165.
[http://dx.doi.org/10.1016/bs.pmbts.2017.04.001] [PMID: 28662830]
[113]
Montagnani M, Quon MJ. Insulin action in vascular endothelium: potential mechanisms linking insulin resistance with hypertension. Diabetes Obes Metab 2000; 2(5): 285-92.
[http://dx.doi.org/10.1046/j.1463-1326.2000.00092.x] [PMID: 11225743]
[114]
Ramsay JE, Ferrell WR, Crawford L, Wallace AM, Greer IA, Sattar N. Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways. J Clin Endocrinol Metab 2002; 87(9): 4231-7.
[http://dx.doi.org/10.1210/jc.2002-020311] [PMID: 12213876]
[115]
Bar J, Kovo M, Schraiber L, Shargorodsky M. Placental maternal and fetal vascular circulation in healthy non-obese and metabolically healthy obese pregnant women. Atherosclerosis 2017; 260: 63-6.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.03.006] [PMID: 28349890]
[116]
Heid ME, Keyel PA, Kamga C, Shiva S, Watkins SC, Salter RD. Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage and inflammasome activation. J Immunol 2013; 191(10): 5230-8.
[http://dx.doi.org/10.4049/jimmunol.1301490] [PMID: 24089192]
[117]
Shimada K, Crother TR, Karlin J, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 2012; 36(3): 401-14.
[http://dx.doi.org/10.1016/j.immuni.2012.01.009] [PMID: 22342844]
[118]
Chen H, Chan DC. Mitochondrial dynamics in mammals. Curr Top Dev Biol 2004; 59: 119-44.
[http://dx.doi.org/10.1016/S0070-2153(04)59005-1] [PMID: 14975249]
[119]
Sun M, Shen W, Zhong M, Wu P, Chen H, Lu A. Nandrolone attenuates aortic adaptation to exercise in rats. Cardiovasc Res 2013; 97(4): 686-95.
[http://dx.doi.org/10.1093/cvr/cvs423] [PMID: 23338851]
[120]
Xu S, Li X, Liu Y, Xia Y, Chang R, Zhang C. Inflammasome inhibitors: promising therapeutic approaches against cancer. J Hematol Oncol 2019; 12(1): 64.
[http://dx.doi.org/10.1186/s13045-019-0755-0] [PMID: 31242947]
[121]
Holen I, Lefley DV, Francis SE, et al. IL-1 drives breast cancer growth and bone metastasis in vivo. Oncotarget 2016; 7(46): 75571-84.
[http://dx.doi.org/10.18632/oncotarget.12289] [PMID: 27765923]
[122]
Bellamy WT, Richter L, Sirjani D, et al. Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. Blood 2001; 97(5): 1427-34.
[http://dx.doi.org/10.1182/blood.V97.5.1427] [PMID: 11222390]
[123]
Nie L, Lyros O, Medda R, et al. Endothelial-mesenchymal transition in normal human esophageal endothelial cells cocultured with esophageal adenocarcinoma cells: role of IL-1β and TGF-β2. Am J Physiol Cell Physiol 2014; 307(9): C859-77.
[http://dx.doi.org/10.1152/ajpcell.00081.2014] [PMID: 25163519]
[124]
Serrano-Martín X, Payares G, Mendoza-León A. Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in ex-perimental murine cutaneous leishmaniasis. Antimicrob Agents Chemother 2006; 50(12): 4214-6.
[http://dx.doi.org/10.1128/AAC.00617-06] [PMID: 17015627]
[125]
Tamura K, Ishikawa G, Yoshie M, et al. Glibenclamide inhibits NLRP3 inflammasome-mediated IL-1β secretion in human trophoblasts. J Pharmacol Sci 2017; 135(2): 89-95.
[http://dx.doi.org/10.1016/j.jphs.2017.09.032] [PMID: 29056256]
[126]
Marchetti C, Chojnacki J, Toldo S, et al. A novel pharmacologic inhibitor of the NLRP3 inflammasome limits myocardial injury after ischemia-reperfusion in the mouse. J Cardiovasc Pharmacol 2014; 63(4): 316-22.
[http://dx.doi.org/10.1097/FJC.0000000000000053] [PMID: 24336017]
[127]
Warren AY, Harvey L, Shaw RW, Khan RN. Interleukin-1 beta secretion from cord blood mononuclear cells in vitro involves P2X 7 receptor activation. Reprod Sci 2008; 15(2): 189-94.
[http://dx.doi.org/10.1177/1933719107310710] [PMID: 18089587]
[128]
Lappas M. Caspase-1 activation is increased with human labour in foetal membranes and myometrium and mediates infection-induced interleukin-1β secretion. Am J Reprod Immunol 2014; 71(2): 189-201.
[http://dx.doi.org/10.1111/aji.12174] [PMID: 24238269]
[129]
Matias ML, Gomes VJ, Romao-Veiga M, et al. Silibinin downregulates the NF-κB pathway and NLRP1/NLRP3 inflammasomes in monocytes from pregnant women with preeclampsia. Molecules 2019; 24(8)E1548
[http://dx.doi.org/10.3390/molecules24081548] [PMID: 31010153]
[130]
Souza CO, Peraçoli MT, Weel IC, et al. Hepatoprotective and anti-inflammatory effects of silibinin on experimental preeclampsia induced by L-NAME in rats. Life Sci 2012; 91(5-6): 159-65.
[http://dx.doi.org/10.1016/j.lfs.2012.06.036] [PMID: 22781706]
[131]
Youm YH, Nguyen KY, Grant RW, et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med 2015; 21(3): 263-9.
[http://dx.doi.org/10.1038/nm.3804] [PMID: 25686106]
[132]
Gan W, Ren J, Li T, et al. The SGK1 inhibitor EMD638683, prevents Angiotensin II-induced cardiac inflammation and fibrosis by blocking NLRP3 inflammasome activation. Biochim Biophys Acta Mol Basis Dis 2018; 1864(1): 1-10.
[http://dx.doi.org/10.1016/j.bbadis.2017.10.001] [PMID: 28986310]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy