{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:17:30Z","timestamp":1789183050267,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Arvid Nilssons Foundation","award":["NFF17SA0030576"],"award-info":[{"award-number":["NFF17SA0030576"]}]},{"name":"Grosserer L.F. Foghts Foundation","award":["NFF17SA0030576"],"award-info":[{"award-number":["NFF17SA0030576"]}]},{"DOI":"10.13039\/501100009708","name":"Aarhus University Hospital","doi-asserted-by":"publisher","award":["NFF17SA0030576"],"award-info":[{"award-number":["NFF17SA0030576"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The John and Birthe Meyer Foundation","award":["NFF17SA0030576"],"award-info":[{"award-number":["NFF17SA0030576"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Complications to preterm birth are numerous, including the presence of a patent ductus arteriosus (PDA). The biological understanding of the PDA is sparse and treatment remains controversial. Herein, we speculate whether the PDA is more than a cardiovascular imbalance, and may be a marker in response to immature core molecular and physiological processes driven by biological systems, such as inflammation. To achieve a new biological understanding of the PDA, we performed echocardiography and collected plasma samples on day 3 of life in 53 consecutively born neonates with a gestational age at birth below 28 completed weeks. The proteome of these samples was analyzed by mass spectrometry (nanoLC-MS\/MS) and immunoassay of 17 cytokines and chemokines. We found differences in 21 proteins and 8 cytokines between neonates with a large PDA (&gt;1.5 mm) compared to neonates without a PDA. Amongst others, we found increased levels of angiotensinogen, periostin, pro-inflammatory associations, including interleukin (IL)-1\u03b2 and IL-8, and anti-inflammatory associations, including IL-1RA and IL-10. Levels of complement factors C8 and carboxypeptidases were decreased. Our findings associate the PDA with the renin-angiotensin-aldosterone system and immune- and complement systems, indicating that PDA goes beyond the persistence of a fetal circulatory connection of the great vessels.<\/jats:p>","DOI":"10.3390\/biom12091179","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T21:28:12Z","timestamp":1661462892000},"page":"1179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Patent Ductus Arteriosus in Extremely Preterm Neonates Is More than a Hemodynamic Challenge: New Molecular Insights"],"prefix":"10.3390","volume":"12","author":[{"given":"Anna","family":"Sellmer","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark"},{"name":"Perinatal Epidemiology Research Unit, Department of Pediatrics, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark"},{"name":"Department of Cardiothoracic Surgery, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine Brink","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark"},{"name":"Perinatal Epidemiology Research Unit, Department of Pediatrics, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Palmfeldt","sequence":"additional","affiliation":[{"name":"Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodil Hammer","family":"Bech","sequence":"additional","affiliation":[{"name":"Department of Public Health, Aarhus University, Bartholins All\u00e9 2, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1081-0675","authenticated-orcid":false,"given":"Julie","family":"Astono","sequence":"additional","affiliation":[{"name":"Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4354-1731","authenticated-orcid":false,"given":"Tue Bjerg","family":"Bennike","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8047-0015","authenticated-orcid":false,"given":"Vibeke Elisabeth","family":"Hjortdal","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1016\/S0140-6736(12)61689-4","article-title":"Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990\u20132010: A systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Murray","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jri.2017.11.003","article-title":"Chronic inflammation and impaired development of the preterm brain","volume":"125","author":"Bennet","year":"2018","journal-title":"J. Reprod. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jpeds.2016.03.058","article-title":"Blood Cytokine Profiles Associated with Distinct Patterns of Bronchopulmonary Dysplasia among Extremely Low Birth Weight Infants","volume":"174","author":"Ambalavanan","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00281-020-00803-2","article-title":"Preterm birth and sustained inflammation: Consequences for the neonate","volume":"42","author":"Humberg","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41390-019-0582-6","article-title":"A perfect storm: Fetal inflammation and the developing immune system","volume":"87","author":"Sabic","year":"2020","journal-title":"Pediatr. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/S0022-3476(96)70192-0","article-title":"Early-onset sepsis in very low birth weight neonates: A report from the National Institute of Child Health and Human Development Neonatal Research Network","volume":"129","author":"Stoll","year":"1996","journal-title":"J. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"113988","DOI":"10.1016\/j.expneurol.2022.113988","article-title":"Perinatal infection, inflammation, preterm birth, and brain injury: A review with proposals for future investigations","volume":"351","author":"Reiss","year":"2022","journal-title":"Exp. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1093\/chromsci\/bmw167","article-title":"Proteomics: Technologies and Their Applications","volume":"55","author":"Aslam","year":"2017","journal-title":"J. Chromatogr. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.cell.2007.07.032","article-title":"Is proteomics the new genomics?","volume":"130","author":"Cox","year":"2007","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Palstrom, N.B., Matthiesen, R., Rasmussen, L.M., and Beck, H.C. (2022). Recent Developments in Clinical Plasma Proteomics-Applied to Cardiovascular Research. Biomedicines, 10.","DOI":"10.3390\/biomedicines10010162"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"F505","DOI":"10.1136\/archdischild-2013-303816","article-title":"Morbidity and mortality in preterm neonates with patent ductus arteriosus on day 3","volume":"98","author":"Sellmer","year":"2013","journal-title":"Arch. Dis. Child.-Fetal Neonatal Ed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.echo.2006.09.001","article-title":"Guidelines and standards for performance of a pediatric echocardiogram: A report from the Task Force of the Pediatric Council of the American Society of Echocardiography","volume":"19","author":"Lai","year":"2006","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0022-3476(78)80282-0","article-title":"Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1500 gm","volume":"92","author":"Papile","year":"1978","journal-title":"J. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105142","DOI":"10.1016\/j.earlhumdev.2020.105142","article-title":"Cardiovascular biomarkers in the evaluation of patent ductus arteriosus in very preterm neonates: A cohort study","volume":"149","author":"Sellmer","year":"2020","journal-title":"Early Hum. Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1021\/acs.jproteome.8b00276","article-title":"Proteomics of the Rat Myocardium during Development of Type 2 Diabetes Mellitus Reveals Progressive Alterations in Major Metabolic Pathways","volume":"17","author":"Edhager","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1074\/mcp.M111.015362","article-title":"Super-SILAC allows classification of diffuse large B-cell lymphoma subtypes by their protein expression profiles","volume":"11","author":"Deeb","year":"2012","journal-title":"Mol. Cell Proteom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"578505","DOI":"10.3389\/fimmu.2020.578505","article-title":"Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life","volume":"11","author":"Bennike","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_18","first-page":"1","article-title":"Fitting Linear Mixed-Effects Models using lme4","volume":"67","author":"Bolker","year":"2015","journal-title":"J. Stat. Softw."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Yoav","year":"1995","journal-title":"J. Royal Stat. Soc. Ser. B"},{"key":"ref_20","unstructured":"R Core Team (2021). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_21","unstructured":"R Studio Team (2015). RStudio: Integrated Development Environment for R, R Studio Team."},{"key":"ref_22","unstructured":"Wickham, H., Fran\u00e7ois, R., Henry, L., and M\u00fcller, K. (2022, July 05). dplyr: A Grammar of Data Manipulation, R Package Version 1.0.7. Available online: https:\/\/dplyr.tidyverse.org\/."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rohart, F., Gautier, B., Singh, A., and KA, L.C. (2017). mixOmics: An R package for \u2018omics feature selection and multiple data integration. PLoS Comput Biol., 13.","DOI":"10.1101\/108597"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_25","unstructured":"Kassambara, A. (2022, July 05). ggpubr: \u2018ggplot2\u2019 Based Publication Ready Plots, R Package Version 0.4.0. Available online: https:\/\/rpkgs.datanovia.com\/ggpubr\/."},{"key":"ref_26","unstructured":"Wilke, C.O. (2022, July 05). Cowplot: Streamlined Plot Theme and Plot Annotations for \u2018ggplot2\u2019, R Package Version 1.1.1. Available online: https:\/\/rdrr.io\/cran\/cowplot\/."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Robin, X., Turck, N., Hainard, A., Tiberti, N., Lisacek, F., Sanchez, J.C., and M\u00fcller, M. (2011). pROC: An open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-77"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Go, H., Ono, J., Ohto, H., Nollet, K.E., Sato, K., Kume, Y., Maeda, H., Chishiki, M., Haneda, K., and Ichikawa, H. (Pediatr. Res., 2021). Can serum periostin predict bronchopulmonary dysplasia in premature infants?, Pediatr. Res., online ahead of print.","DOI":"10.21203\/rs.3.rs-100219\/v1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1164\/rccm.201605-0910LE","article-title":"Early Elevation of Plasma Periostin Is Associated with Chronic Ventilator-Dependent Bronchopulmonary Dysplasia","volume":"194","author":"Ahlfeld","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/hr.2016.17","article-title":"Structure and functions of angiotensinogen","volume":"39","author":"Lu","year":"2016","journal-title":"Hypertens Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1053\/j.gastro.2005.07.055","article-title":"STAT3 NH2-terminal acetylation is activated by the hepatic acute-phase response and required for IL-6 induction of angiotensinogen","volume":"129","author":"Ray","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S1357-2725(02)00271-6","article-title":"Inflammation and angiotensin II","volume":"35","author":"Suzuki","year":"2003","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1203\/00006450-200209000-00004","article-title":"Angiotensin converting enzyme inhibition decreases cell turnover in the neonatal rat heart","volume":"52","author":"Choi","year":"2002","journal-title":"Pediatr. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.tips.2008.05.003","article-title":"Role of the renin-angiotensin system in vascular inflammation","volume":"29","author":"Marchesi","year":"2008","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s11906-018-0900-0","article-title":"Inflammation as a Regulator of the Renin-Angiotensin System and Blood Pressure","volume":"20","author":"Satou","year":"2018","journal-title":"Curr. Hypertens Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/oby.20626","article-title":"Cord blood levels of osteopontin as a phenotype marker of gestational age and neonatal morbidities","volume":"22","author":"Joung","year":"2014","journal-title":"Obesity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/s11883-009-0032-8","article-title":"Osteopontin: A multifunctional protein at the crossroads of inflammation, atherosclerosis, and vascular calcification","volume":"11","author":"Cho","year":"2009","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_39","first-page":"1450","article-title":"Macrophages express osteopontin during repair of myocardial necrosis","volume":"145","author":"Murry","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1091\/mbc.3.10.1169","article-title":"Expression and distribution of osteopontin in human tissues: Widespread association with luminal epithelial surfaces","volume":"3","author":"Brown","year":"1992","journal-title":"Mol. Biol. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"F708","DOI":"10.1152\/ajprenal.2000.278.5.F708","article-title":"Angiotensinogen and AT(1) antisense inhibition of osteopontin translation in rat proximal tubular cells","volume":"278","author":"Ricardo","year":"2000","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1046\/j.1523-1755.2001.00032.x","article-title":"Expression, roles, receptors, and regulation of osteopontin in the kidney","volume":"60","author":"Xie","year":"2001","journal-title":"Kidney Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1046\/j.1523-1755.2000.00309.x","article-title":"Osteopontin expression in progressive renal injury in remnant kidney: Role of angiotensin II","volume":"58","author":"Yu","year":"2000","journal-title":"Kidney Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1161\/CIRCULATIONAHA.118.035047","article-title":"IL (Interleukin)-10-STAT3-Galectin-3 Axis Is Essential for Osteopontin-Producing Reparative Macrophage Polarization After Myocardial Infarction","volume":"138","author":"Shirakawa","year":"2018","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Shirakawa, K., and Sano, M. (2021). Osteopontin in Cardiovascular Diseases. Biomolecules, 11.","DOI":"10.3390\/biom11071047"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jpeds.2012.02.007","article-title":"Urine biomarkers predict acute kidney injury in newborns","volume":"161","author":"Askenazi","year":"2012","journal-title":"J. Pediatr."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kany, S., Vollrath, J.T., and Relja, B. (2019). Cytokines in Inflammatory Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20236008"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1359-6101(02)00020-5","article-title":"The balance between IL-1 and IL-1Ra in disease","volume":"13","author":"Arend","year":"2002","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12621","article-title":"Overview of the IL-1 family in innate inflammation and acquired immunity","volume":"281","author":"Dinarello","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"701375","DOI":"10.3389\/fcvm.2021.701375","article-title":"Congenital Heart Disease: An Immunological Perspective","volume":"8","author":"Singampalli","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"19671971","DOI":"10.1007\/s10741-021-10187-6","article-title":"Immunity and inflammation: The neglected key players in congenital heart disease?","volume":"27","author":"Wienecke","year":"2022","journal-title":"Heart Fail. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"925314","DOI":"10.3389\/fcvm.2022.925314","article-title":"Increased inflammatory markers in adult patients born with an atrial septal defect","volume":"9","author":"Schram","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fped.2020.00040","article-title":"Right Atrial Myocardial Remodeling in Children With Atrial Septal Defect Involves Inflammation, Growth, Fibrosis, and Apoptosis","volume":"8","author":"Rouatbi","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1002\/prca.201400166","article-title":"Acute phase proteins altered in the plasma of patients with congenital ventricular septal defect","volume":"9","author":"Zhang","year":"2015","journal-title":"Proteom. Clin. Appl."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41390-018-0182-x","article-title":"Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22\u201327 weeks\u2019 gestation","volume":"86","author":"Olsson","year":"2019","journal-title":"Pediatr. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/pr.2013.238","article-title":"Intermittent or sustained systemic inflammation and the preterm brain","volume":"75","author":"Dammann","year":"2014","journal-title":"Pediatr. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1203\/00006450-199606000-00007","article-title":"Undetectable interleukin (IL)-10 and persistent IL-8 expression early in hyaline membrane disease: A possible developmental basis for the predisposition to chronic lung inflammation in preterm newborns","volume":"39","author":"Jones","year":"1996","journal-title":"Pediatr. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"155343","DOI":"10.1016\/j.cyto.2020.155343","article-title":"Interleukin 8 may predict surgical necrotizing enterocolitis in infants born less than 1500 g","volume":"137","author":"Seo","year":"2021","journal-title":"Cytokine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.bbi.2020.09.007","article-title":"Interleukin-8 dysregulation is implicated in brain dysmaturation following preterm birth","volume":"90","author":"Sullivan","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s11481-018-9804-7","article-title":"Executive Dysfunction Early Postnatal Biomarkers among Children Born Extremely Preterm","volume":"14","author":"Leviton","year":"2019","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.15252\/embj.201591881","article-title":"Complement activation, regulation, and molecular basis for complement-related diseases","volume":"34","author":"Bajic","year":"2015","journal-title":"Embo J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6842","DOI":"10.1002\/jcp.27433","article-title":"Altered plasma proteins released from platelets and endothelial cells are associated with human patent ductus arteriosus","volume":"234","author":"Hou","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_63","first-page":"295","article-title":"Immunological profile in congenital heart disease","volume":"31","author":"Khalil","year":"1994","journal-title":"Indian Pediatr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/sji.12154","article-title":"Complement profile in neonates of different gestational ages","volume":"79","author":"Grumach","year":"2014","journal-title":"Scand. J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1007\/s00018-013-1494-y","article-title":"The role of periostin in tissue remodeling across health and disease","volume":"71","author":"Conway","year":"2014","journal-title":"Cell Mol. Life Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1093\/cvr\/cvx039","article-title":"Periostin paves the way for neonatal heart regeneration","volume":"113","author":"Hudson","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2174\/138920208786847917","article-title":"Periostin as a heterofunctional regulator of cardiac development and disease","volume":"9","author":"Conway","year":"2008","journal-title":"Curr. Genom."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/bdra.23149","article-title":"Periostin downregulation is an early marker of inhibited neonatal murine lung alveolar septation","volume":"97","author":"Ahlfeld","year":"2013","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Bozyk, P.D., Bentley, J.K., Popova, A.P., Anyanwu, A.C., Linn, M.D., Goldsmith, A.M., Pryhuber, G.S., Moore, B.B., and Hershenson, M.B. (2012). Neonatal periostin knockout mice are protected from hyperoxia-induced alveolar simplication. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031336"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1093\/cvr\/cvx001","article-title":"Ablation of periostin inhibits post-infarction myocardial regeneration in neonatal mice mediated by the phosphatidylinositol 3 kinase\/glycogen synthase kinase 3beta\/cyclin D1 signalling pathway","volume":"113","author":"Chen","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/00365513.2011.626868","article-title":"Soluble CD163","volume":"72","author":"Moller","year":"2012","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1182\/blood.V99.1.378","article-title":"Identification of the hemoglobin scavenger receptor\/CD163 as a natural soluble protein in plasma","volume":"99","author":"Peterslund","year":"2002","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1089\/ars.2012.4834","article-title":"CD163 and inflammation: Biological, diagnostic, and therapeutic aspects","volume":"18","author":"Etzerodt","year":"2013","journal-title":"Antioxid Redox Signal"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1039\/C8MO00239H","article-title":"Degradation of the extracellular matrix is part of the pathology of ulcerative colitis","volume":"15","author":"Kirov","year":"2019","journal-title":"Mol. 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