{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T23:00:42Z","timestamp":1778886042359,"version":"3.51.4"},"reference-count":61,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VA BLR&D Merit Review Award","award":["I01 BX004263"],"award-info":[{"award-number":["I01 BX004263"]}]},{"DOI":"10.13039\/100008294","name":"Louisiana State University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008294","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH National Heart, Lung, and Blood Institute R01 grants","award":["HL102167"],"award-info":[{"award-number":["HL102167"]}]},{"name":"NIH National Heart, Lung, and Blood Institute R01 grants","award":["HL119291"],"award-info":[{"award-number":["HL119291"]}]},{"name":"NIH National Heart, Lung, and Blood Institute R01 grants","award":["1R01AA029690-01A1"],"award-info":[{"award-number":["1R01AA029690-01A1"]}]},{"name":"NIH National Heart, Lung, and Blood Institute R01 grants","award":["HL133053"],"award-info":[{"award-number":["HL133053"]}]},{"name":"NIH National Institute of Alcoholism and Abuse grants","award":["AA027662"],"award-info":[{"award-number":["AA027662"]}]},{"name":"National Center for Advancing Translational Sciences of the National Institutes of Health","award":["UL1TR002378"],"award-info":[{"award-number":["UL1TR002378"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pulmonary hypertension (PH) causes morbidity and mortality in sickle cell disease (SCD). The release of heme during hemolysis triggers endothelial dysfunction and contributes to PH. Long non-coding RNAs (lncRNAs) may play a pivotal role in endothelial dysfunction and PH pathogenesis. This study assessed the regulatory role of the lncRNA\u2013heme oxygenase-1 (HMOX1) axis in SCD-associated PH pathogenesis. Total RNAs were isolated from the lungs of 15\u201317-week-old sickle cell (SS) mice and littermate controls (AA) mice and subjected to lncRNA expression profiling using the Arrystar\u2122 lncRNA array. Volcano plot filtering was used to screen for differentially expressed lncRNAs and mRNAs with statistical significance (fold change &gt; 1.8, p &lt; 0.05). A total of 3915 lncRNAs were upregulated and a total of 3545 lncRNAs were downregulated in the lungs of SS mice compared to AA mice. To validate differentially expressed lncRNAs, six upregulated lncRNAs and six downregulated lncRNAs were selected for quantitative PCR. MALAT1 expression was significantly upregulated in the lungs of SS mice and in hemin-treated human pulmonary artery endothelial cells (HPAECs), suggesting that hemolysis induces MALAT1. Functional studies revealed that MALAT1 depletion increased, while MALAT1 overexpression decreased, the endothelial dysfunction markers endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM1), indicating a protective role of MALAT1 in maintaining endothelial homeostasis. In vivo, adenoviral MALAT1 overexpression attenuated PH, right ventricular hypertrophy (RVH), vascular remodeling, and reduced ET-1 and VCAM1 expression in SS mice. Given that HMOX1 protects endothelial cells during hemolysis, we observed that HMOX1 expression and activity were elevated in SS mouse lungs and hemin-treated HPAECs. HMOX1 knockdown enhanced ET-1 and VCAM1 expression, confirming its endothelial-protective function. Importantly, MALAT1 overexpression increased HMOX1 expression and activity, whereas MALAT1 knockdown reduced HMOX1 levels and mRNA stability. Collectively, these findings identify MALAT1 as a protective regulator that mitigates endothelial dysfunction, vascular remodeling, and PH in SCD, at least in part through the induction of HMOX1. These results suggest that SCD modulates the MALAT1\u2013HMOX1 axis, and further characterization of MALAT1 function may provide new insights into SCD-associated endothelial dysfunction and PH pathogenesis, as well as identify novel therapeutic targets.<\/jats:p>","DOI":"10.3390\/cells15020154","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:13:21Z","timestamp":1768475601000},"page":"154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Long Non-Coding RNA MALAT1 Regulates HMOX1 in Sickle Cell Disease-Associated Pulmonary Hypertension"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-5900","authenticated-orcid":false,"given":"Viranuj","family":"Sueblinvong","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah S.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Atlanta Veterans Affairs Healthcare System, Decatur, GA 30033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Atlanta Veterans Affairs Healthcare System, Decatur, GA 30033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9185-0865","authenticated-orcid":false,"given":"David R.","family":"Archer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Hematology, Oncology, and BMT, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solomon","family":"Ofori-Acquah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Hematology, Oncology, and BMT, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8628-6975","authenticated-orcid":false,"given":"Roy L.","family":"Sutliff","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changwon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Louisiana State University Health Science Center, Shreveport, LA 71103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Michael","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Atlanta Veterans Affairs Healthcare System, Decatur, GA 30033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin T.","family":"Kopp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pulmonology, Asthma, Cystic Fibrosis, and Sleep Medicine, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8251-1637","authenticated-orcid":false,"given":"Bum-Yong","family":"Kang","sequence":"additional","affiliation":[{"name":"Atlanta Veterans Affairs Healthcare System, Decatur, GA 30033, USA"},{"name":"Department of Pediatrics, Division of Pulmonology, Asthma, Cystic Fibrosis, and Sleep Medicine, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1378\/chest.117.3.796","article-title":"Mortality from Primary Pulmonary Hypertension in the United States, 1979\u20131996","volume":"117","author":"Lilienfeld","year":"2000","journal-title":"Chest"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1056\/NEJM199406093302303","article-title":"Mortality in Sickle Cell Disease. Life Expectancy and Risk Factors for Early Death","volume":"330","author":"Platt","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/00005792-198801000-00005","article-title":"Sickle Cell Chronic Lung Disease: Prior Morbidity and the Risk of Pulmonary Failure","volume":"67","author":"Powars","year":"1988","journal-title":"Medicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1016\/S0140-6736(10)61029-X","article-title":"Sickle-Cell Disease","volume":"376","author":"Rees","year":"2010","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1001\/archinte.1974.00320160118010","article-title":"Hemolysis in Sickle Cell Disease","volume":"133","author":"Bensinger","year":"1974","journal-title":"Arch. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1182\/blood-2005-06-2373","article-title":"Lactate Dehydrogenase as a Biomarker of Hemolysis-Associated Nitric Oxide Resistance, Priapism, Leg Ulceration, Pulmonary Hypertension, and Death in Patients with Sickle Cell Disease","volume":"107","author":"Kato","year":"2006","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1056\/NEJM199306173282402","article-title":"Expression of Endothelin-1 in the Lungs of Patients with Pulmonary Hypertension","volume":"328","author":"Giaid","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1161\/CIRCULATIONAHA.104.503540","article-title":"Pulmonary Arterial Hypertension","volume":"114","author":"McLaughlin","year":"2006","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"464","DOI":"10.7326\/0003-4819-114-6-464","article-title":"Increased Plasma Endothelin-1 in Pulmonary Hypertension: Marker or Mediator of Disease?","volume":"114","author":"Stewart","year":"1991","journal-title":"Ann. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1161\/01.CIR.84.6.2280","article-title":"Plasma Endothelin Concentrations in Patients with Pulmonary Hypertension Associated with Congenital Heart Defects. Evidence for Increased Production of Endothelin in Pulmonary Circulation","volume":"84","author":"Yoshibayashi","year":"1991","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1164\/ajrccm.156.1.9611085","article-title":"Endothelin-1 Production During the Acute Chest Syndrome in Sickle Cell Disease","volume":"156","author":"Hammerman","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1182\/blood.V92.7.2594","article-title":"Increased Levels of Endothelin-1 in Plasma of Sickle Cell Anemia Patients","volume":"92","author":"Rybicki","year":"1998","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/(SICI)1096-8652(199807)58:3<195::AID-AJH6>3.0.CO;2-M","article-title":"Elevated Plasma Endothelin-1 Levels in Sickle Cell Anemia: Relationships to Oxygen Saturation and Left Ventricular Hypertrophy","volume":"58","author":"Werdehoff","year":"1998","journal-title":"Am. J. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/332411a0","article-title":"A Novel Potent Vasoconstrictor Peptide Produced by Vascular Endothelial Cells","volume":"332","author":"Yanagisawa","year":"1988","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1111\/j.1365-2141.2009.07906.x","article-title":"Endothelin Receptor Antagonists for Pulmonary Hypertension in Adult Patients with Sickle Cell Disease","volume":"147","author":"Minniti","year":"2009","journal-title":"Br. J. Haematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/s41440-019-0378-4","article-title":"Malat1: A Therapeutic Candidate for a Broad Spectrum of Vascular and Cardiorenal Complications","volume":"43","author":"Puthanveetil","year":"2020","journal-title":"Hypertens. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sun, Y., and Ma, L. (2019). New Insights into Long Non-Coding Rna Malat1 in Cancer and Metastasis. Cancers, 11.","DOI":"10.3390\/cancers11020216"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.vph.2018.03.003","article-title":"Long Non-Coding Rnas in Vascular Biology and Disease","volume":"114","author":"Jae","year":"2019","journal-title":"Vascul. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.14735\/amko20193S65","article-title":"Long Non-Coding Rnas\u2014Current Methods of Detection and Clinical Applications","volume":"32","author":"Moranova","year":"2019","journal-title":"Klin. Onkol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00438-017-1370-9","article-title":"Gene Regulation of Mammalian Long Non-Coding Rna","volume":"293","author":"Bunch","year":"2018","journal-title":"Mol. Genet. Genomics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"eadd2029","DOI":"10.1126\/scitranslmed.add2029","article-title":"Allele-specific Control of Rodent and Human Lncrna Kmt2e-As1 Promotes Hypoxic Endothelial Pathology in Pulmonary Hypertension","volume":"16","author":"Tai","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1093\/cvr\/cvaa050","article-title":"Pathobiology of Pulmonary Artery Hypertension: Role of Long Non-Coding Rnas","volume":"116","author":"Zahid","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8031","DOI":"10.1038\/sj.onc.1206928","article-title":"MALAT-1, a Novel Noncoding Rna, and Thymosin Beta4 Predict Metastasis and Survival in Early-Stage Non-Small Cell Lung Cancer","volume":"22","author":"Ji","year":"2003","journal-title":"Oncogene"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1515\/cclm-2016-0056","article-title":"Functional Polymorphism of Lncrna Malat1 Contributes to Pulmonary Arterial Hypertension Susceptibility in Chinese People","volume":"55","author":"Zhuo","year":"2017","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1182\/blood-2017-12-819870","article-title":"HO-1(Hi) Patrolling Monocytes Protect Against Vaso-Occlusion in Sickle Cell Disease","volume":"131","author":"Liu","year":"2018","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R23-29","DOI":"10.1172\/JCI6163","article-title":"Hypoxia Induces Severe Right Ventricular Dilatation and Infarction in Heme Oxygenase-1 Null Mice","volume":"103","author":"Yet","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8798","DOI":"10.1073\/pnas.161272598","article-title":"Targeted Expression of Heme Oxygenase-1 Prevents the Pulmonary Inflammatory and Vascular Responses to Hypoxia","volume":"98","author":"Minamino","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1189\/jlb.0708445","article-title":"Altered Levels of Cytokines and Inflammatory Mediators in Plasma and Leukocytes of Sickle Cell Anemia Patients and Effects of Hydroxyurea Therapy","volume":"85","author":"Lanaro","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ghosh, S., Tan, F., Yu, T., Li, Y., Adisa, O., Mosunjac, M., and Ofori-Acquah, S.F. (2011). Global Gene Expression Profiling of Endothelium Exposed to Heme Reveals an Organ-Specific Induction of Cytoprotective Enzymes in Sickle Cell Disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018399"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1182\/blood-2006-02-004812","article-title":"Correction of Sickle Cell Disease by Homologous Recombination in Embryonic Stem Cells","volume":"108","author":"Wu","year":"2006","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1165\/rcmb.2016-0166OC","article-title":"Peroxisome Proliferator-Activated Receptor Gamma Regulates the V-Ets Avian Erythroblastosis Virus E26 Oncogene Homolog 1\/Microrna-27a Axis to Reduce Endothelin-1 and Endothelial Dysfunction in the Sickle Cell Mouse Lung","volume":"56","author":"Kang","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1165\/rcmb.2008-0132OC","article-title":"Rosiglitazone Attenuates Chronic Hypoxia-Induced Pulmonary Hypertension in a Mouse Model","volume":"42","author":"Nisbet","year":"2010","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1165\/rcmb.2014-0337OC","article-title":"Peroxisome Proliferator-Activated Receptor Gamma and Microrna 98 in Hypoxia-Induced Endothelin-1 Signaling","volume":"54","author":"Kang","year":"2016","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"L881","DOI":"10.1152\/ajplung.00195.2011","article-title":"The Ppargamma Ligand Rosiglitazone Attenuates Hypoxia-Induced Endothelin Signaling in Vitro and in Vivo","volume":"301","author":"Kang","year":"2011","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1182\/bloodadvances.2020002754","article-title":"Ppargamma Increases Huwe1 to Attenuate Nf-Kappab\/P65 and Sickle Cell Disease with Pulmonary Hypertension","volume":"5","author":"Jang","year":"2021","journal-title":"Blood Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ncrna.2016.11.002","article-title":"Long Non-Coding Rnas: Mechanism of Action and Functional Utility","volume":"1","author":"Bhat","year":"2016","journal-title":"Noncoding RNA Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1177\/1535370216685434","article-title":"Analysis of Hypoxia-Induced Noncoding Rnas Reveals Metastasis-Associated Lung Adenocarcinoma Transcript 1 as an Important Regulator of Vascular Smooth Muscle Cell Proliferation","volume":"242","author":"Brock","year":"2017","journal-title":"Exp. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kurakula, K., Smolders, V., Tura-Ceide, O., Jukema, J.W., Quax, P.H.A., and Goumans, M.J. (2021). Endothelial Dysfunction in Pulmonary Hypertension: Cause or Consequence?. Biomedicines, 9.","DOI":"10.3390\/biomedicines9010057"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1038\/s41375-018-0067-3","article-title":"Drugging the Lncrna Malat1 Via Lna Gapmer Aso Inhibits Gene Expression of Proteasome Subunits and Triggers Anti-Multiple Myeloma Activity","volume":"32","author":"Amodio","year":"2018","journal-title":"Leukemia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1161\/CIRCRESAHA.114.303265","article-title":"Long Noncoding Rna Malat1 Regulates Endothelial Cell Function and Vessel Growth","volume":"114","author":"Michalik","year":"2014","journal-title":"Circ. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8418","DOI":"10.1093\/nar\/gkac630","article-title":"Intratracheally Administered Lna Gapmer Antisense Oligonucleotides Induce Robust Gene Silencing in Mouse Lung Fibroblasts","volume":"50","author":"Shin","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.canlet.2021.04.020","article-title":"Mettl3 Enhances the Stability of Malat1 with the Assistance of Hur Via M6a Modification and Activates Nf-Kappab to Promote the Malignant Progression of Idh-Wildtype Glioma","volume":"511","author":"Chang","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kang, B.Y., Park, K.K., Green, D.E., Bijli, K.M., Searles, C.D., Sutliff, R.L., and Hart, C.M. (2013). Hypoxia Mediates Mutual Repression between Microrna-27a and Ppargamma in the Pulmonary Vasculature. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079503"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"L559","DOI":"10.1152\/ajplung.00090.2010","article-title":"Ppar{Gamma} Regulates Hypoxia-Induced Nox4 Expression in Human Pulmonary Artery Smooth Muscle Cells through Nf-{Kappa}B","volume":"299","author":"Lu","year":"2010","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1172\/JCI33452","article-title":"Molecular Pathogenesis of Pulmonary Arterial Hypertension","volume":"118","author":"Rabinovitch","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1182\/blood-2006-08-039438","article-title":"Hemolysis in Sickle Cell Mice Causes Pulmonary Hypertension Due to Global Impairment in Nitric Oxide Bioavailability","volume":"109","author":"Hsu","year":"2007","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhang, P., Nguyen, J., Abdulla, F., Nelson, A.T., Beckman, J.D., Vercellotti, G.M., and Belcher, J.D. (2021). Soluble Md-2 and Heme in Sickle Cell Disease Plasma Promote Pro-Inflammatory Signaling in Endothelial Cells. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.632709"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"L314","DOI":"10.1152\/ajplung.00252.2014","article-title":"Vasculopathy and Pulmonary Hypertension in Sickle Cell Disease","volume":"308","author":"Potoka","year":"2015","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/nm1202-799","article-title":"Cell-Free Hemoglobin Limits Nitric Oxide Bioavailability in Sickle-Cell Disease","volume":"8","author":"Reiter","year":"2002","journal-title":"Nat. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/FJC.0000000000000570","article-title":"New Nitric Oxide Donor Ncx 1443: Therapeutic Effects on Pulmonary Hypertension in the Sad Mouse Model of Sickle Cell Disease","volume":"71","author":"Abid","year":"2018","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/stem.548","article-title":"Mesenchymal Stromal Cells Expressing Heme Oxygenase-1 Reverse Pulmonary Hypertension","volume":"29","author":"Liang","year":"2011","journal-title":"Stem Cells"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Yachie, A. (2021). Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041514"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/jpsu.2003.50172","article-title":"Expression of Heme Oxygenase-1 and Endothelial Nitric Oxide Synthase in the Lung of Newborns with Congenital Diaphragmatic Hernia and Persistent Pulmonary Hypertension","volume":"38","author":"Solari","year":"2003","journal-title":"J. Pediatr. Surg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"149470","DOI":"10.1016\/j.gene.2025.149470","article-title":"MicroRNAs in sickle cell disease: A comprehensive review","volume":"957","author":"Gupta","year":"2025","journal-title":"Gene"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3194","DOI":"10.1074\/jbc.M110.148726","article-title":"Regulation of Heme Oxygenase-1 Protein Expression by Mir-377 in Combination with Mir-217","volume":"286","author":"Beckman","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.bbagrm.2012.06.001","article-title":"The Let-7 Microrna Enhances Heme Oxygenase-1 by Suppressing Bach1 and Attenuates Oxidant Injury in Human Hepatocytes","volume":"1819","author":"Hou","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1016\/j.freeradbiomed.2011.09.014","article-title":"Heme Oxygenase 1 Is Induced by Mir-155 Via Reduced Bach1 Translation in Endothelial Cells","volume":"51","author":"Pulkkinen","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1089\/gtmb.2020.0034","article-title":"The Circular Rna Cdr1as Regulates the Proliferation and Apoptosis of Human Cardiomyocytes through the Mir-135a\/Hmox1 and Mir-135b\/Hmox1 Axes","volume":"24","author":"Chen","year":"2020","journal-title":"Genet. Test. Mol. 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