{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T21:47:43Z","timestamp":1784238463288,"version":"3.55.0"},"reference-count":67,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austrian Science Fund (FWF)","award":["DOC 31-B26"],"award-info":[{"award-number":["DOC 31-B26"]}]},{"name":"the Medical University of Graz","award":["DOC 31-B26"],"award-info":[{"award-number":["DOC 31-B26"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hydroxychloroquine (HCQ), an anti-malarial drug, is suggested as a promising candidate for the treatment of pregnancy-related disorders associated with endothelial activation, among which there is preeclampsia (PE). Arterial feto-placental endothelial cells (fpECAs) were isolated from control (CTR) and early-onset preeclamptic (EO-PE) placentas. The aim of this study was to test potential protective effects of HCQ in an in vitro model of endothelial activation as well as in cells isolated from EO-PE placentas. To mimic PE conditions, CTR fpECAs were exposed to a pro-inflammatory environment consisting of tumor necrosis factor \u03b1 (TNF-\u03b1), interleukin (IL)-6 and IL-1\u03b2 (furtherly referred as MIX) with or without varying concentrations of HCQ (1 \u00b5g\/mL and 10 \u00b5g\/mL). Their effect on wound healing and endothelial barrier integrity was analyzed. Variations in the expression of IL-8 and leukocyte adhesion molecules (LAM) on both mRNA and protein levels were determined between CTR and PE fpECAs in the presence or absence of HCQ. MIX decreased wound healing and stability of the endothelial barrier, but HCQ did not affect it. Significant differences between CTR and EO-PE fpECAs were observed in IL-8 mRNA, protein secretion, and vascular cell adhesion protein 1 (VCAM-1) mRNA expression levels. After challenging CTR fpECAs with MIX, upregulation of both mRNA and protein levels was observed in all molecules. Combined treatment of HCQ and MIX slightly lowered VCAM-1 total protein amount. In CTR fpECAs, treatment with low concentrations of HCQ alone (1 \u00b5g\/mL) reduced basal levels of IL-8 and VCAM-1 mRNA and secretion of IL-8, while in EO-PE fpECAs, a higher (10\u00b5g\/mL) HCQ concentration slightly reduced the gene expression of IL-8. Conclusion: These results provide additional support for the safety of HCQ, as it did not adversely affect endothelial functionality in control fpECAs at the tested concentration. Furthermore, the observed limited effects on IL-8 secretion in EO-PE fpECAs warrant further investigation, highlighting the need for clinical trials to assess the potential therapeutic effects of HCQ in preeclampsia. Conducting clinical trials would offer a more comprehensive understanding of HCQ\u2019s efficacy and safety, allowing us to explore its potential benefits and limitations in a real-world clinical setting.<\/jats:p>","DOI":"10.3390\/ijms241310934","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T16:06:37Z","timestamp":1688141197000},"page":"10934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Impact of Hydroxychloroquine on Primary Feto-Placental Endothelial Cells from Healthy and Early-Onset Preeclamptic Placentas"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5213-2641","authenticated-orcid":false,"given":"Maja","family":"Gaji\u0107","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5996-2373","authenticated-orcid":false,"given":"Bianca","family":"Schr\u00f6der-Heurich","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Horvat Mercnik","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mila","family":"Cervar-Zivkovic","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-8642","authenticated-orcid":false,"given":"Christian","family":"Wadsack","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria"},{"name":"BioTechMed-Graz, Mozartgasse 12\/II, A-8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1924-5695","authenticated-orcid":false,"given":"Frauke","family":"von Versen-H\u00f6ynck","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany"},{"name":"Department of Obstetrics and Gynecology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3077-108X","authenticated-orcid":false,"given":"Karoline","family":"Mayer-Pickel","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1136\/annrheumdis-2019-216656","article-title":"Efficacy of pharmacological treatment in rheumatoid arthritis: A systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis","volume":"79","author":"Kerschbaumer","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1136\/annrheumdis-2019-215213","article-title":"EULAR recommendations for the management of antiphospholipid syndrome in adults","volume":"78","author":"Tektonidou","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1097\/BOR.0000000000000096","article-title":"Advances in the understanding and treatment of systemic complications in Sj\u00f6gren\u2019s syndrome","volume":"26","year":"2014","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1007\/s10067-017-3822-3","article-title":"Primary Sj\u00f6gren\u2019s syndrome: Extraglandular manifestations and hydroxychloroquine therapy","volume":"36","author":"Demarchi","year":"2017","journal-title":"Clin. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wang, S.-Q., Zhang, L.-W., Wei, P., and Hua, H. (2017). Is hydroxychloroquine effective in treating primary Sjogren\u2019s syndrome: A systematic review and meta-analysis. BMC Musculoskelet. Disord., 18.","DOI":"10.1186\/s12891-017-1543-z"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1080\/14740338.2017.1269168","article-title":"Hydroxychloroquine in systemic lupus erythematosus (SLE)","volume":"16","author":"Ponticelli","year":"2017","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10787-015-0239-y","article-title":"Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases","volume":"23","author":"Rainsford","year":"2015","journal-title":"Inflammopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s12016-016-8596-x","article-title":"Tumor Necrosis Factor-Alpha and Pregnancy: Focus on Biologics. An Updated and Comprehensive Review","volume":"53","author":"Llurba","year":"2017","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.biopha.2018.08.027","article-title":"Immunomodulatory effects of hydroxychloroquine on Th1\/Th2 balance in women with repeated implantation failure","volume":"107","author":"Hajshafiha","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1517\/14740338.2011.566555","article-title":"Hydroxychloroquine in systemic lupus erythematosus and rheumatoid arthritis and its safety in pregnancy","volume":"10","author":"Abarientos","year":"2011","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e000651","DOI":"10.1136\/lupus-2021-000651","article-title":"Hydroxychloroquine in the pregnancies of women with lupus: A meta-analysis of individual participant data","volume":"9","author":"Clowse","year":"2022","journal-title":"Lupus Sci. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1055\/s-0039-3402752","article-title":"Does Hydroxychloroquine Protect against Preeclampsia and Preterm Delivery in Systemic Lupus Erythematosus Pregnancies?","volume":"37","author":"Do","year":"2020","journal-title":"Am. J. Perinatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2810202","DOI":"10.1155\/2017\/2810202","article-title":"Hydroxychloroquine Use in Lupus Patients during Pregnancy Is Associated with Longer Pregnancy Duration in Preterm Births","volume":"2017","author":"Kroese","year":"2017","journal-title":"J. Immunol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1002\/art.11304","article-title":"Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: A study of one hundred thirty-three cases compared with a control group","volume":"48","author":"Amoura","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/bcp.12872","article-title":"Reproductive outcomes following hydroxychloroquine use for autoimmune diseases: A systematic review and meta-analysis","volume":"81","author":"Kaplan","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1161\/HYPERTENSIONAHA.114.03587","article-title":"Chronic Hydroxychloroquine Improves Endothelial Dysfunction and Protects Kidney in a Mouse Model of Systemic Lupus Erythematosus","volume":"64","author":"Romero","year":"2014","journal-title":"Hypertension"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/14767058.2017.1289511","article-title":"Treatment of preeclampsia with hydroxychloroquine: A review","volume":"31","author":"DeKoninck","year":"2018","journal-title":"J. Matern. Fetal. Neonatal Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/bcp.14131","article-title":"Hydroxychloroquine may be beneficial in preeclampsia and recurrent miscarriage","volume":"86","author":"Alavi","year":"2020","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.1017\/erm.2022.18","article-title":"TNF-\u03b1\/anti-TNF-\u03b1 drugs and its effect on pregnancy outcomes","volume":"24","author":"Dai","year":"2022","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.placenta.2010.12.005","article-title":"TNF-\u03b1 inhibits trophoblast integration into endothelial cellular networks","volume":"32","author":"Xu","year":"2011","journal-title":"Placenta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1067\/mob.2003.134","article-title":"Increased vascular endothelial cell production of interleukin-6 in severe preeclampsia","volume":"188","author":"Takacs","year":"2003","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1177\/1933719116641760","article-title":"Serum Levels of TNF-\u03b1 and IL-6 Are Associated with Pregnancy-Induced Hypertension","volume":"23","author":"Li","year":"2016","journal-title":"Reprod. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e15080","DOI":"10.1097\/MD.0000000000015080","article-title":"Immune imbalance is associated with the development of preeclampsia","volume":"98","author":"Ma","year":"2019","journal-title":"Medicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/imm.12757","article-title":"Association between cytokine profile and transcription factors produced by T-cell subsets in early- and late-onset pre-eclampsia","volume":"152","author":"Ribeiro","year":"2017","journal-title":"Immunology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1089\/jir.2012.0013","article-title":"Placental Secretion of Interleukin-1 and Interleukin-1 Receptor Antagonist in Preeclampsia: Effect of Magnesium Sulfate","volume":"32","author":"Amash","year":"2012","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3109\/10641955.2014.931419","article-title":"Expression of lipoxin A4, TNF\u03b1 and IL-1\u03b2 in maternal peripheral blood, umbilical cord blood and placenta, and their significance in pre-eclampsia","volume":"33","author":"Dong","year":"2014","journal-title":"Hypertens. Pregnancy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.2741\/2243","article-title":"Endothelial barrier function in preeclampsia","volume":"12","author":"Wang","year":"2007","journal-title":"Front. Biosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1001\/jama.285.12.1607","article-title":"Association of Maternal Endothelial Dysfunction with Preeclampsia","volume":"285","author":"Chambers","year":"2001","journal-title":"JAMA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7084","DOI":"10.1080\/14767058.2021.1943656","article-title":"Effect of hydroxychloroquine on antiphospholipid antibodies-inhibited endometrial angiogenesis","volume":"35","author":"Dong","year":"2022","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"219","DOI":"10.15171\/bi.2017.26","article-title":"Effect of hydroxychloroquine on oxidative\/nitrosative status and angiogenesis in endothelial cells under high glucose condition","volume":"7","author":"Rezabakhsh","year":"2017","journal-title":"Bioimpacts"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s13075-019-1935-6","article-title":"A novel function of artesunate on inhibiting migration and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients","volume":"21","author":"Ma","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_32","first-page":"237","article-title":"Activation of endothelial cells in preeclampsia: Increased neutrophil\u2013endothelial adhesion correlates with up-regulation of adhesion molecule P-selectin in human umbilical vein endothelial cells isolated from preeclampsia","volume":"5","author":"Wang","year":"1998","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.preghy.2019.09.002","article-title":"CYP1A1, GSTT1, IL-6 and IL-8 transcription and IL-6 secretion on umbilical endothelial cells from hypertensive pregnant women: Preliminary results","volume":"18","author":"Albores","year":"2019","journal-title":"Pregnancy Hypertens."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1111\/j.1432-0436.2008.00302.x","article-title":"Human fetal placental endothelial cells have a mature arterial and a juvenile venous phenotype with adipogenic and osteogenic differentiation potential","volume":"76","author":"Lang","year":"2008","journal-title":"Differentiation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s41581-019-0119-6","article-title":"Pre-eclampsia: Pathogenesis, novel diagnostics and therapies","volume":"15","author":"Phipps","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.4049\/jimmunol.155.3.1428","article-title":"IL-8 induces neutrophil chemotaxis predominantly via type I IL-8 receptors","volume":"155","author":"Hammond","year":"1995","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1172\/JCI114265","article-title":"Neutrophil-activating peptide-1\/interleukin 8, a novel cytokine that activates neutrophils","volume":"84","author":"Baggiolini","year":"1989","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"155828","DOI":"10.1016\/j.cyto.2022.155828","article-title":"Interleukin-8: An evolving chemokine","volume":"153","author":"Matsushima","year":"2022","journal-title":"Cytokine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/1477-7827-9-124","article-title":"Serum leptin levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in normal pregnancy and preeclampsia","volume":"9","author":"Molvarec","year":"2011","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cyto.2013.02.027","article-title":"Severe preeclampsia goes along with a cytokine network disturbance towards a systemic inflammatory state","volume":"62","author":"Pinheiro","year":"2013","journal-title":"Cytokine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/1043-4666(92)90085-6","article-title":"The effect of second-line antirheumatic drugs on interleukin-8 mRNA synthesis and protein secretion in human endothelial cells","volume":"4","author":"Deleuran","year":"1992","journal-title":"Cytokine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10175","DOI":"10.1038\/s41598-022-14571-6","article-title":"Effect of add-on hydroxychloroquine therapy on serum proinflammatory cytokine levels in patients with systemic lupus erythematosus","volume":"12","author":"Wakiya","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s10787-018-0512-y","article-title":"Efficacy analysis of hydroxychloroquine therapy in systemic lupus erythematosus: A study on disease activity and immunological biomarkers","volume":"26","author":"Monzavi","year":"2018","journal-title":"Inflammopharmacology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1177\/0961203312437270","article-title":"Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: Data from LUMINA (LXXV), a multiethnic US cohort","volume":"21","author":"Willis","year":"2012","journal-title":"Lupus"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Viloti\u0107, A., Nacka-Aleksi\u0107, M., Pirkovi\u0107, A., Boji\u0107-Trbojevi\u0107, Z., Dekanski, D., and Krivoku\u0107a, M.J. (2022). IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314574"},{"key":"ref_46","first-page":"283","article-title":"NF-kappa B is activated during acute inflammation in vivo in association with elevated endothelial cell adhesion molecule gene expression and leukocyte recruitment","volume":"45","author":"Manning","year":"1995","journal-title":"J. Inflamm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1146\/annurev.cellbio.042308.113238","article-title":"Rolling Cell Adhesion","volume":"26","author":"McEver","year":"2010","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.4049\/jimmunol.1400571","article-title":"Identification of Activators of ERK5 Transcriptional Activity by High-Throughput Screening and the Role of Endothelial ERK5 in Vasoprotective Effects Induced by Statins and Antimalarial Agents","volume":"193","author":"Le","year":"2014","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.intimp.2018.08.008","article-title":"Attenuation of antimalarial agent hydroxychloroquine on TNF-\u03b1-induced endothelial inflammation","volume":"63","author":"Li","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kadife, E., Hannan, N., Harper, A., Binder, N., Beard, S., and Brownfoot, F.C. (2022). Hydroxychloroquine reduces soluble Flt-1 secretion from human cytotrophoblast, but does not mitigate markers of endothelial dysfunction in vitro. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0271560"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"102555","DOI":"10.1016\/j.autrev.2020.102555","article-title":"Hydroxychloroquine reduces IL-6 and pro-thrombotic status","volume":"19","author":"Sciascia","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.preghy.2016.09.001","article-title":"The effects of hydroxychloroquine on endothelial dysfunction","volume":"6","author":"Rahman","year":"2016","journal-title":"Pregnancy Hypertens."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e000681","DOI":"10.1136\/lupus-2022-000681","article-title":"Influence of hydroxychloroquine blood levels on adhesion molecules associated with endothelial dysfunction in patients with systemic lupus erythematosus","volume":"9","author":"Fasano","year":"2022","journal-title":"Lupus Sci. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e000602","DOI":"10.1136\/lupus-2021-000602","article-title":"Hydroxychloroquine PK and exposure-response in pregnancies with lupus: The importance of adherence for neonatal outcomes","volume":"9","author":"Balevic","year":"2022","journal-title":"Lupus Sci. Med."},{"key":"ref_55","first-page":"4108271","article-title":"Early- and Late-Onset Preeclampsia: A Comprehensive Cohort Study of Laboratory and Clinical Findings according to the New ISHHP Criteria","volume":"2019","author":"Babczyk","year":"2019","journal-title":"Int. J. Hypertens."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"544.e1","DOI":"10.1016\/j.ajog.2013.08.019","article-title":"Incidence of preeclampsia: Risk factors and outcomes associated with early- versus late-onset disease","volume":"209","author":"Lisonkova","year":"2013","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1161\/HYPERTENSIONAHA.112.198366","article-title":"Unique Blood Pressure Characteristics in Mother and Offspring after Early Onset Preeclampsia","volume":"60","author":"Lazdam","year":"2012","journal-title":"Hypertension"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1067\/S0002-9378(03)00576-3","article-title":"The frequency and severity of placental findings in women with preeclampsia are gestational age dependent","volume":"189","author":"Moldenhauer","year":"2003","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.preghy.2012.11.001","article-title":"The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP)","volume":"3","author":"Tranquilli","year":"2013","journal-title":"Pregnancy Hypertens."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0140-6736(08)60074-4","article-title":"Epidemiology and causes of preterm birth","volume":"371","author":"Goldenberg","year":"2008","journal-title":"Lancet"},{"key":"ref_61","unstructured":"(2019). ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet. Gynecol., 133, 1."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.cyto.2011.09.021","article-title":"A meta-analysis of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 in preeclampsia","volume":"56","author":"Xie","year":"2011","journal-title":"Cytokine"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.placenta.2014.03.016","article-title":"IL-1\u03b2 and TGF-\u03b2 weaken the placental barrier through destruction of tight junctions: An in vivo and in vitro study","volume":"35","author":"Tossetta","year":"2014","journal-title":"Placenta"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1136\/ard.2006.067835","article-title":"Very low blood hydroxychloroquine concentration as an objective marker of poor adherence to treatment of systemic lupus erythematosus","volume":"66","author":"Amoura","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1136\/annrheumdis-2012-202322","article-title":"Hydroxychloroquine in systemic lupus erythematosus: Results of a French multicentre controlled trial (PLUS Study)","volume":"72","author":"Galicier","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Miatmoko, A., Hendrianto, E., Karsari, D., Dinaryanti, A., Ertanti, N., Ihsan, I.S., Purnama, D.S., and Asmarawati, T.P. (2021). An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and\/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0252302"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Suarez-Arnedo, A., Torres Figueroa, F., Clavijo, C., Arbel\u00e1ez, P., Cruz, J.C., and Mu\u00f1oz-Camargo, C. (2020). An image J plugin for the high throughput image analysis of in vitro scratch wound healing assays. PLoS ONE, 15.","DOI":"10.1101\/2020.04.20.050831"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10934\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:03:52Z","timestamp":1760126632000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10934"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,30]]},"references-count":67,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241310934"],"URL":"https:\/\/doi.org\/10.3390\/ijms241310934","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,30]]}}}