{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T19:03:22Z","timestamp":1777575802768,"version":"3.51.4"},"reference-count":59,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T00:00:00Z","timestamp":1715990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI21\/01244"],"award-info":[{"award-number":["PI21\/01244"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["P2022-BMD\/7321"],"award-info":[{"award-number":["P2022-BMD\/7321"]}]},{"name":"European Union","award":["PI21\/01244"],"award-info":[{"award-number":["PI21\/01244"]}]},{"name":"European Union","award":["P2022-BMD\/7321"],"award-info":[{"award-number":["P2022-BMD\/7321"]}]},{"name":"Madrid\u2019s community","award":["PI21\/01244"],"award-info":[{"award-number":["PI21\/01244"]}]},{"name":"Madrid\u2019s community","award":["P2022-BMD\/7321"],"award-info":[{"award-number":["P2022-BMD\/7321"]}]},{"name":"ProACapital","award":["PI21\/01244"],"award-info":[{"award-number":["PI21\/01244"]}]},{"name":"ProACapital","award":["P2022-BMD\/7321"],"award-info":[{"award-number":["P2022-BMD\/7321"]}]},{"name":"HALE KULANI, S.L. and MJR.","award":["PI21\/01244"],"award-info":[{"award-number":["PI21\/01244"]}]},{"name":"HALE KULANI, S.L. and MJR.","award":["P2022-BMD\/7321"],"award-info":[{"award-number":["P2022-BMD\/7321"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC\u2014apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain\u2014caspase 1, caspase 5, caspase 8, and interleukin 1\u03b2) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations.<\/jats:p>","DOI":"10.3390\/ijms25105528","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T08:20:31Z","timestamp":1716193231000},"page":"5528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy"],"prefix":"10.3390","volume":"25","author":[{"given":"Mar\u00eda Asunci\u00f3n","family":"S\u00e1nchez-Gil","sequence":"first","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"University Defense Center of Madrid (CUD), 28047 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4494-6397","authenticated-orcid":false,"given":"Oscar","family":"Fraile-Martinez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cielo","family":"Garc\u00eda-Montero","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"De Leon-Oliva","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego Liviu","family":"Boaru","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"De Castro-Martinez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adr\u00edan","family":"Camacho-Alc\u00e1zar","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6320-2668","authenticated-orcid":false,"given":"Juan A.","family":"De Le\u00f3n-Luis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coral","family":"Bravo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0412-939X","authenticated-orcid":false,"given":"Ra\u00fal","family":"D\u00edaz-Pedrero","sequence":"additional","affiliation":[{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"L\u00f3pez-Gonzalez","sequence":"additional","affiliation":[{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Pathological Anatomy Service, University Hospital G\u00f3mez-Ulla, 28806 Alcala de Henares, 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Deutsch. Dermatol. Ges."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.avsg.2014.10.009","article-title":"Biomolecular Mechanisms in Varicose Veins Development","volume":"29","author":"Segiet","year":"2015","journal-title":"Ann. Vasc. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., Fraile-Mart\u00ednez, O., Garc\u00eda-Montero, C., \u00c1lvarez-Mon, M.A., Chaowen, C., Ruiz-Grande, F., Pekarek, L., Monserrat, J., As\u00fansolo, A., and Garc\u00eda-Honduvilla, N. (2021). Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management. J. Clin. Med., 10.","DOI":"10.3390\/jcm10153239"},{"key":"ref_4","first-page":"138","article-title":"Chronic Venous Disease during Pregnancy\u2014Servier\u2014PhlebolymphologyServier\u2014Phlebolymphology","volume":"21","author":"Boivin","year":"2014","journal-title":"Phlebolymphology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jvsv.2017.08.001","article-title":"The Hemodynamic Effects of Pregnancy on the Lower Extremity Venous System","volume":"6","author":"Taylor","year":"2018","journal-title":"J. Vasc. Surg. Venous Lymphat. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., S\u00e1nchez-Trujillo, L., Bravo, C., Fraile-Martinez, O., Garc\u00eda-Montero, C., Saez, M.A., Alvarez-Mon, M.A., Sainz, F., Alvarez-Mon, M., and Bujan, J. (2021). Newborns of Mothers with Venous Disease during Pregnancy Show Increased Levels of Lipid Peroxidation and Markers of Oxidative Stress and Hypoxia in the Umbilical Cord. Antioxidants, 10.","DOI":"10.3390\/antiox10060980"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., Saez, M.A., Fraile-Mart\u00ednez, O., As\u00fansolo, \u00c1., Pekarek, L., Bravo, C., Coca, S., Sainz, F., \u00c1lvarez-Mon, M., and Buj\u00e1n, J. (2020). Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072487"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., G\u00f3mez-Lahoz, A.M., S\u00e1nchez-Trujillo, L., Fraile-Martinez, O., Garc\u00eda-Montero, C., Guijarro, L.G., Bravo, C., De Leon-Luis, J.A., Saz, J.V., and Bujan, J. (2022). Chronic Venous Disease during Pregnancy Causes a Systematic Increase in Maternal and Fetal Proinflammatory Markers. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23168976"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.7150\/ijms.58992","article-title":"Abnormal Proinflammatory and Stressor Environmental with Increased the Regulatory Cellular IGF-1\/PAPP-A\/STC and Wnt-1\/\u03b2-Catenin Canonical Pathway in Placenta of Women with Chronic Venous Disease during Pregnancy","volume":"18","author":"Ortega","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Trujillo, L., Fraile-Martinez, O., Garc\u00eda-Montero, C., Garc\u00eda-Puente, L.M., Guijarro, L.G., De Leon-Oliva, D., Boaru, D.L., Gard\u00f3n-Alburquerque, D., del Val Toledo Lobo, M., and Royuela, M. (2023). Chronic Venous Disease during Pregnancy Is Related to Inflammation of the Umbilical Cord: Role of Allograft Inflammatory Factor 1 (AIF-1) and Interleukins 10 (IL-10), IL-12 and IL-18. J. Pers. Med., 13.","DOI":"10.3390\/jpm13060956"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.4049\/jimmunol.1900901","article-title":"Inflammasomes: Their Role in Normal and Complicated Pregnancies","volume":"203","author":"Motomura","year":"2019","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"555826","DOI":"10.3389\/fimmu.2020.555826","article-title":"NLRP3 Inflammasome and Its Critical Role in Gynecological Disorders and Obstetrical Complications","volume":"11","author":"Fang","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Gil, M.A., Fraile-Martinez, O., Garc\u00eda-Montero, C., Toledo, M.D.V., Guijarro, L.G., De Le\u00f3n-Luis, J.A., Bravo, C., D\u00edaz-Pedrero, R., L\u00f3pez-Gonzalez, L., and Saez, M.A. (2024). Histopathological Clues of Enhanced Inflammation in the Placental Tissue of Women with Chronic Venous Disease in Lower Limbs during Pregnancy. J. Pers. Med., 14.","DOI":"10.3390\/jpm14010087"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1177\/039463200902200208","article-title":"Inflammasomes are differentially expressed in cardiovascular and other tissues","volume":"22","author":"Yin","year":"2009","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1160\/TH13-10-0860","article-title":"Inflammation and peripheral venous disease. The San Diego Population Study","volume":"112","author":"Cushman","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Trujillo, L., Garc\u00eda-Montero, C., Fraile-Martinez, O., Guijarro, L.G., Bravo, C., De Leon-Luis, J.A., Saez, J.V., Bujan, J., Alvarez-Mon, M., and Garc\u00eda-Honduvilla, N. (2022). Considering the Effects and Maternofoetal Implications of Vascular Disorders and the Umbilical Cord. Medicina, 58.","DOI":"10.3390\/medicina58121754"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.avsg.2017.06.131","article-title":"The Role of Endothelial Dysfunction and Inflammation in Chronic Venous Disease","volume":"46","author":"Cardoso","year":"2018","journal-title":"Ann. Vasc. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., Chaowen, C., Fraile-Martinez, O., Garc\u00eda-Montero, C., Saez, M.A., Cruza, I., Pereda-Cerquella, C., Alvarez-Mon, M.A., Guijarro, L.G., and Fatych, Y. (2022). Chronic Venous Disease in Pregnant Women Causes an Increase in ILK in the Placental Villi Associated with a Decrease in E-Cadherin. J. Pers. Med., 12.","DOI":"10.3390\/jpm12020277"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.4103\/ijves.ijves_71_20","article-title":"Chronic Venous Insufficiency in Pregnant Women","volume":"8","author":"Patnaik","year":"2021","journal-title":"Indian J. Vasc. Endovasc. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Socha, M.W., Malinowski, B., Puk, O., Dubiel, M., and Wici\u0144ski, M. (2020). The NLRP3 Inflammasome Role in the Pathogenesis of Pregnancy Induced Hypertension and Preeclampsia. Cells, 9.","DOI":"10.20944\/preprints202005.0357.v1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1007\/s11033-020-05345-2","article-title":"Comprehensive Review of ASC Structure and Function in Immune Homeostasis and Disease","volume":"47","author":"Agrawal","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/CM9.0000000000001214","article-title":"NLRP3 Inflammasome: A New Therapeutic Target for High-Risk Reproductive Disorders?","volume":"134","author":"Zhou","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1232629","DOI":"10.3389\/fimmu.2023.1232629","article-title":"Reframing the Link between Metabolism and NLRP3 Inflammasome: Therapeutic Opportunities","volume":"14","author":"Ortega","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.humpath.2018.03.022","article-title":"Placentas from Women with Pregnancy-Associated Venous Insufficiency Show Villi Damage with Evidence of Hypoxic Cellular Stress","volume":"77","author":"Ortega","year":"2018","journal-title":"Hum. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Montero, C., Fraile-Martinez, O., Rodriguez-Mart\u00edn, S., Funes Mo\u00f1ux, R.M., Saz, J.V., Bravo, C., De Leon-Luis, J.A., Ruiz-Minaya, M., Pekarek, L., and Saez, M.A. (2022). Irregular Expression of Cellular Stress Response Markers in the Placenta of Women with Chronic Venous Disease. Antioxidants, 11.","DOI":"10.3390\/antiox11112277"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"879021","DOI":"10.3389\/fnagi.2022.879021","article-title":"The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases","volume":"14","author":"Blevins","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4157","DOI":"10.1111\/jcmm.15077","article-title":"Pregnancy-Associated Venous Insufficiency Course with Placental and Systemic Oxidative Stress","volume":"24","author":"Ortega","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.jaci.2023.09.020","article-title":"Hypoxia-Inducible Factor 1\u03b1 Activates the NLRP3 Inflammasome to Regulate Epithelial Differentiation in Chronic Rhinosinusitis","volume":"152","author":"Zhong","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1538\/expanim.21-0002","article-title":"PI3K Regulates the Activation of NLRP3 Inflammasome in Atherosclerosis through Part-Dependent AKT Signaling Pathway","volume":"70","author":"Liu","year":"2021","journal-title":"Exp. Anim."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1177\/002215540104901009","article-title":"Expression of Apoptosis-Associated Speck-like Protein Containing a Caspase Recruitment Domain, a Pyrin N-Terminal Homology Domain-Containing Protein, in Normal Human Tissues","volume":"49","author":"Masumoto","year":"2001","journal-title":"J. Histochem. Cytochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.4049\/jimmunol.1301676","article-title":"Apoptosis-Associated Speck-like Protein Containing a CARD Forms Specks but Does Not Activate Caspase-1 in the Absence of NLRP3 during Macrophage Swelling","volume":"194","author":"Compan","year":"2015","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-3-319-39406-0_4","article-title":"Apoptotic Caspases in Promoting Cancer: Implications from Their Roles in Development and Tissue Homeostasis","volume":"930","author":"Dabrowska","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.tcb.2017.01.003","article-title":"Post-Translational Modification of Caspases: The Other Side of Apoptosis Regulation","volume":"27","author":"Zamaraev","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1093\/humupd\/dmu059","article-title":"A Clear and Present Danger: Inflammasomes DAMPing down Disorders of Pregnancy","volume":"21","author":"Khan","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1080\/14767050802212109","article-title":"Evidence of the Involvement of Caspase-1 under Physiologic and Pathologic Cellular Stress during Human Pregnancy: A Link Between the Inflammasome and Parturition","volume":"21","author":"Gotsch","year":"2008","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.immuni.2015.06.003","article-title":"Proteolytic Processing of Interleukin-1 Family Cytokines: Variations on a Common Theme","volume":"42","author":"Afonina","year":"2015","journal-title":"Immunity"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tapia, V.S., Daniels, M.J.D., Palaz\u00f3n-Riquelme, P., Dewhurst, M., Luheshi, N.M., Rivers-Auty, J., Green, J., Redondo-Castro, E., Kaldis, P., and Lopez-Castejon, G. (2019). The Three Cytokines IL-1\u03b2, IL-18, and IL-1\u03b1 Share Related but Distinct Secretory Routes. J. Biol. Chem., 294.","DOI":"10.1074\/jbc.RA119.008009"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5589","DOI":"10.1111\/bph.12876","article-title":"IL\u20131\u03b2 and IL\u201318: Inflammatory Markers or Mediators of Hypertension?","volume":"171","author":"Krishnan","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1111\/cei.12608","article-title":"Interleukin-1 Family Cytokines and Their Regulatory Proteins in Normal Pregnancy and Pre-Eclampsia","volume":"181","author":"Southcombe","year":"2015","journal-title":"Clin. Exp. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"103583","DOI":"10.1016\/j.jri.2022.103583","article-title":"The Cytokines IL-1b and IL-18 Are Upregulated in the Placenta of Recurrent Miscarriage Patients","volume":"158","author":"Vilsmaier","year":"2023","journal-title":"J. Reprod. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.immuni.2018.07.017","article-title":"Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development","volume":"49","author":"Yockey","year":"2018","journal-title":"Immunity"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"C784","DOI":"10.1152\/ajpcell.00503.2023","article-title":"Pyroptosis in Health and Disease","volume":"326","author":"Imre","year":"2024","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/imr.12534","article-title":"Molecular Mechanisms and Functions of Pyroptosis, Inflammatory Caspases and Inflammasomes in Infectious Diseases","volume":"277","author":"Man","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/s41419-019-2162-4","article-title":"Pyroptosis Is a Critical Inflammatory Pathway in the Placenta from Early Onset Preeclampsia and in Human Trophoblasts Exposed to Hypoxia and Endoplasmic Reticulum Stressors","volume":"10","author":"Cheng","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"103214","DOI":"10.1016\/j.jri.2020.103214","article-title":"NLRP3 Inflammasome Function and Pyroptotic Cell Death in Human Placental Hofbauer Cells","volume":"142","author":"Abrahams","year":"2020","journal-title":"J. Reprod. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mandal, R., Barr\u00f3n, J.C., Kostova, I., Becker, S., and Strebhardt, K. (2020). Caspase-8: The Double-Edged Sword. Biochim. Biophys. Acta (BBA) Rev. Cancer, 1873.","DOI":"10.1016\/j.bbcan.2020.188357"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.4049\/jimmunol.2000226","article-title":"Noncanonical Roles of Caspase-4 and Caspase-5 in Heme-Driven IL-1\u03b2 Release and Cell Death","volume":"206","author":"Rohrman","year":"2021","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.4049\/jimmunol.2000373","article-title":"Function and Regulation of Noncanonical Caspase-4\/5\/11 Inflammasome","volume":"204","author":"Matikainen","year":"2020","journal-title":"J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.4110\/in.2018.18.e41","article-title":"Regulatory Roles of the Caspase-11 Non-Canonical Inflammasome in Inflammatory Diseases","volume":"18","author":"Yi","year":"2018","journal-title":"Immune Netw."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ajpath.2014.08.025","article-title":"Novel Roles for Caspase-8 in IL-1\u03b2 and Inflammasome Regulation","volume":"185","author":"Gurung","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Belousova, V., Svitich, O., Timokhina, E., Ignatko, I., Bogomazova, I., Pesegova, S., Silaeva, T., Kuzmina, T., and Skorobogatova, O. (2023). Caspase-3, Caspase-8 and XIAP Gene Expression in the Placenta: Exploring the Causes of Spontaneous Preterm Labour. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021692"},{"key":"ref_53","first-page":"27","article-title":"Pathogenesis of Preeclampsia: Implications of Apoptotic Markers and Oxidative Stress","volume":"32","author":"Salman","year":"2013","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Garcia-Puente, L.M., Fraile-Martinez, O., Garc\u00eda-Montero, C., Bujan, J., De Le\u00f3n-Luis, J.A., Bravo, C., Rodr\u00edguez-Benitez, P., Pintado, P., Ruiz-Labarta, F.J., and \u00c1lvarez-Mon, M. (2023). Placentas from Women with Late-Onset Preeclampsia Exhibit Increased Expression of the NLRP3 Inflammasome Machinery. Biomolecules, 13.","DOI":"10.3390\/biom13111644"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jvsv.2019.12.075","article-title":"The 2020 Update of the CEAP Classification System and Reporting Standards","volume":"8","author":"Lurie","year":"2020","journal-title":"J. Vasc. Surg. Venous Lymphat. Disord."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"186","DOI":"10.7150\/ijms.65419","article-title":"Overexpression of glycolysis markers in placental tissue of pregnant women with chronic venous disease: A histological study","volume":"19","author":"Ortega","year":"2022","journal-title":"Int. J. Med. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nprot.2006.83","article-title":"The Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate-Phenol-Chloroform Extraction: Twenty-Something Years On","volume":"1","author":"Chomczynski","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.5713\/ajas.20.0238","article-title":"TATA Box Binding Protein and Ribosomal Protein 4 Are Suitable Reference Genes for Normalization during Quantitative Polymerase Chain Reaction Study in Bovine Mesenchymal Stem Cells","volume":"33","author":"Jang","year":"2020","journal-title":"Asian-Australas. J. Anim. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E66","DOI":"10.1210\/jc.2012-2609","article-title":"Immunoreactivity Score Using an Anti-Sst2A Receptor Monoclonal Antibody Strongly Predicts the Biochemical Response to Adjuvant Treatment with Somatostatin Analogs in Acromegaly","volume":"98","author":"Gatto","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5528\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:44:36Z","timestamp":1760107476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,18]]},"references-count":59,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25105528"],"URL":"https:\/\/doi.org\/10.3390\/ijms25105528","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,18]]}}}