{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:45:42Z","timestamp":1791992742178,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["k99hl177608\u201001"],"award-info":[{"award-number":["k99hl177608\u201001"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01\u2010HL159862"],"award-info":[{"award-number":["R01\u2010HL159862"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01\u2010HL158076"],"award-info":[{"award-number":["R01\u2010HL158076"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01\u2010HL161004"],"award-info":[{"award-number":["R01\u2010HL161004"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32HL007171\u201047"],"award-info":[{"award-number":["T32HL007171\u201047"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pulm. circ."],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Pulmonary hypertension (PH) is a fatal sequela in sickle cell disease (SCD) patients and occurs with greater prevalence compared to the general population. Macrophages (M\u03d5) are one of the first immune cells to be recruited to the lungs in mouse models of PH, including SCD\u2010PH, and a key cell type that contribute toward disease progression. Here, we first determined if phenotypic difference exist between control (C57BL\/6) and Berkeley\u2010SS (Berk\u2010SS, SCD) mouse pulmonary M\u03d5s and, if so, how chronic moderate hypoxic exposure (~8,000\u2009ft, Pb ~568\u2009mmHg for 10 weeks) altered molecular and metabolic pathways. Next, we aimed to determine if the microenvironment of the Berk\u2010SS lung is primed for M\u03d5s recruitment compared to the C57BL\/6 lung. Using precision cut lung slice (PCLS), we determined PCLS from Berk\u2010SS mice have significant increases in adhesion molecules associate with M\u03d5 recruitment and recruit splenic M\u03d5s at a greater rate compared to control mice. We confirmed these results in an acute hypoxic exposure (18,000\u2009ft for 3 days) experiment and our results suggest that Berk\u2010SS mice recruit more interstitial M\u03d5 with a pro\u2010inflammatory phenotype when compared to C57BL\/6 mice. Lastly, the depletion of M\u03d5 in our Berk\u2010SS PH model improved right ventricular function, decreased pulmonary vascular muscularization, and improved exercise tolerance. Together, these data emphasize a critical role of M\u03d5 pulmonary recruitment in SCD\u2010PH pathophysiology that is driven by inflammation.<\/jats:p>","DOI":"10.1002\/pul2.70413","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:53:17Z","timestamp":1791989597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophages Contribute to Pulmonary Hypertension Associated With Sickle Cell Disease"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6217-4063","authenticated-orcid":false,"given":"Christina","family":"Lisk","sequence":"first","affiliation":[{"name":"Cardiovascular and Pulmonary Research Laboratory, Department of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-2150","authenticated-orcid":false,"given":"Francesca","family":"Cendali","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Research Laboratory, Department of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5329-4554","authenticated-orcid":false,"given":"Natalie","family":"Westover","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Research Laboratory, Department of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5521-6518","authenticated-orcid":false,"given":"Delaney","family":"Swindle","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Research Laboratory, Department of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2385-125X","authenticated-orcid":false,"given":"Daniel Colon","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"Section of Pediatric Critical Care Medicine, Department of Pediatrics University of Colorado Denver \u2010 Anschutz Medical Campus and Children's Hospital Colorado Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6113-7815","authenticated-orcid":false,"given":"Caitlin","family":"Lewis","sequence":"additional","affiliation":[{"name":"Section of Pediatric Critical Care Medicine, Department of Pediatrics University of Colorado Denver \u2010 Anschutz Medical Campus and Children's Hospital Colorado Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1619-6322","authenticated-orcid":false,"given":"Melissa J.","family":"Lucero","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Research Laboratory, Department of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4255-977X","authenticated-orcid":false,"given":"Nishant K.","family":"Rana","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Research Laboratory, Department of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4518-0629","authenticated-orcid":false,"given":"Gemlyn","family":"George","sequence":"additional","affiliation":[{"name":"Division of Hematology Colorado Sickle Cell Treatment and Research Center, School of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9874-6948","authenticated-orcid":false,"given":"Saini","family":"Setua","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Blood Oxygen Transport University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Dzieciatkowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Genetics, Graduate School University of Colorado, Anschutz, Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1779-6386","authenticated-orcid":false,"given":"Kathryn","family":"Hassel","sequence":"additional","affiliation":[{"name":"Division of Hematology Colorado Sickle Cell Treatment and Research Center, School of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6830-6522","authenticated-orcid":false,"given":"Christy S.","family":"Niemeyer","sequence":"additional","affiliation":[{"name":"Neurology Department, School of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6918-6411","authenticated-orcid":false,"given":"Kurt","family":"Stenmark","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Research Laboratory, Department of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"},{"name":"Department of Pediatrics University of Colorado \u2010 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7229-5528","authenticated-orcid":false,"given":"Eva","family":"Nozik","sequence":"additional","affiliation":[{"name":"Section of Pediatric Critical Care Medicine, Department of Pediatrics University of Colorado Denver \u2010 Anschutz Medical Campus and Children's Hospital Colorado Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2258-6490","authenticated-orcid":false,"given":"Angelo","family":"D'Alessandro","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Genetics, Graduate School University of Colorado, Anschutz, Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-3008","authenticated-orcid":false,"given":"Paul W.","family":"Buehler","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Research Laboratory, Department of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"},{"name":"Department of Pathology University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Research Laboratory, Department of Medicine University of Colorado Denver \u2010 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"issue":"1","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"R119","DOI":"10.1093\/hmg\/ddab004","article-title":"Evolutionary History of Sickle\u2010Cell Mutation: Implications for Global Genetic Medicine","volume":"30","author":"Esoh K.","year":"2021","journal-title":"Human Molecular Genetics"},{"issue":"2","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1177\/003335491312800206","article-title":"Mortality Rates and Age at Death From Sickle Cell Disease: U.S., 1979\u20132005","volume":"128","author":"Lanzkron S.","year":"2013","journal-title":"Public Health Reports\u00ae"},{"key":"e_1_2_12_4_1","volume-title":"Sickle Cell Disease (Archived)","author":"Sedrak A.","year":"2026"},{"issue":"11","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1055\/a-2145-4648","article-title":"Die neue Definition und Klassifikation der Pulmonalen Hypertonie","volume":"77","author":"Douschan P.","year":"2023","journal-title":"Pneumologie"},{"issue":"7","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24076333","article-title":"Role of Macrophages in Sickle Cell Disease Erythrophagocytosis and Erythropoiesis","volume":"24","author":"Sesti\u2010Costa R.","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"issue":"15","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.127860","article-title":"An Hb\u2010Mediated Circulating Macrophage Contributing to Pulmonary Vascular Remodeling in Sickle Cell Disease","volume":"4","author":"Redinus K.","year":"2019","journal-title":"JCI Insight"},{"issue":"6","key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/MOH.0000000000000836","article-title":"Heme\u2010 and Iron\u2010Activated Macrophages in Sickle Cell Disease: An Updated Perspective","volume":"31","author":"Navaneethabalakrishnan S.","year":"2024","journal-title":"Current Opinion in Hematology"},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1742761","article-title":"Iron Homeostasis and Macrophage Polarization in Pulmonary Fibrosis: Mechanisms and Therapeutic Perspectives","volume":"16","author":"Luo M.","year":"2025","journal-title":"Frontiers in Immunology"},{"issue":"12","key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1001\/jama.2012.358","article-title":"Mortality in Adults With Sickle Cell Disease and Pulmonary Hypertension","volume":"307","author":"Mehari A.","year":"2012","journal-title":"Journal of the American Medical Association"},{"issue":"4","key":"e_1_2_12_11_1","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.02308-2018","article-title":"CCR2\/CCR5\u2010mediated Macrophage\u2010Smooth Muscle Cell Crosstalk in Pulmonary Hypertension","volume":"54","author":"Abid S.","year":"2019","journal-title":"European Respiratory Journal"},{"issue":"5","key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1164\/rccm.202110-2274OC","article-title":"Macrophage\u2010NLRP3 Activation Promotes Right Ventricle Failure in Pulmonary Arterial Hypertension","volume":"206","author":"Al\u2010Qazazi R.","year":"2022","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"issue":"1","key":"e_1_2_12_13_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-11435-x","article-title":"Sotatercept Analog Suppresses Inflammation to Reverse Experimental Pulmonary Arterial Hypertension","volume":"12","author":"Joshi S. R.","year":"2022","journal-title":"Scientific Reports"},{"issue":"2","key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.4049\/jimmunol.1303048","article-title":"Adventitial Fibroblasts Induce a Distinct Proinflammatory\/Profibrotic Macrophage Phenotype in Pulmonary Hypertension","volume":"193","author":"El Kasmi K. C.","year":"2014","journal-title":"Journal of Immunology"},{"issue":"12","key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.4049\/jimmunol.1601692","article-title":"A Time\u2010 and Compartment\u2010Specific Activation of Lung Macrophages in Hypoxic Pulmonary Hypertension","volume":"198","author":"Pugliese S. C.","year":"2017","journal-title":"Journal of Immunology"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2023.1151268","article-title":"Metabolic Correlates to Critical Speed in Murine Models of Sickle Cell Disease","volume":"14","author":"Cendali F. I.","year":"2023","journal-title":"Frontiers in Physiology"},{"key":"e_1_2_12_17_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2025.118595","article-title":"Combined Haptoglobin and Hemopexin Therapy for the Treatment of Cardiopulmonary Dysfunction in Sickle Cell Disease","volume":"192","author":"Lucero M. J.","year":"2025","journal-title":"Biomedicine & Pharmacotherapy"},{"issue":"9","key":"e_1_2_12_18_1","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1182\/bloodadvances.2025018680","article-title":"Ferroportin Inhibition Attenuates Pulmonary Hypertension in Hypoxic Sickle Cell Disease Mice","volume":"10","author":"Lucero M. J.","year":"2026","journal-title":"Blood Advances"},{"key":"e_1_2_12_19_1","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2023.1149005","article-title":"Moderate Hypoxia Induces Metabolic Divergence in Circulating Monocytes and Tissue Resident Macrophages From Berkeley Sickle Cell Anemia Mice","volume":"10","author":"Lisk C.","year":"2023","journal-title":"Frontiers in Medicine"},{"key":"e_1_2_12_20_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-1-4939-9236-2_2","article-title":"High\u2010Throughput Metabolomics: Isocratic and Gradient Mass Spectrometry\u2010Based Methods","volume":"1978","author":"Nemkov T.","year":"2019","journal-title":"Methods in Molecular Biology"},{"key":"e_1_2_12_21_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.freeradbiomed.2021.08.238","article-title":"Hemopexin Dosing Improves Cardiopulmonary Dysfunction in Murine Sickle Cell Disease","volume":"175","author":"Buehler P. 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K.","year":"2019","journal-title":"Journal of Physiology"},{"issue":"1","key":"e_1_2_12_26_1","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the Gap Between Raw Spectra and Functional Insights","volume":"49","author":"Pang Z.","year":"2021","journal-title":"Nucleic Acids Research"},{"issue":"1","key":"e_1_2_12_27_1","doi-asserted-by":"crossref","first-page":"W527","DOI":"10.1093\/nar\/gkac376","article-title":"OmicsNet 2.0: A Web\u2010Based Platform for Multi\u2010Omics Integration and Network Visual Analytics","volume":"50","author":"Zhou G.","year":"2022","journal-title":"Nucleic Acids Research"},{"issue":"9","key":"e_1_2_12_28_1","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines11092413","article-title":"A Review of the Relationship Between the Immune Response, Inflammation, Oxidative Stress, and the Pathogenesis of Sickle Cell Anaemia","volume":"11","author":"Aboderin F. 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