{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T22:59:35Z","timestamp":1784069975656,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/18\/1\/33234"],"award-info":[{"award-number":["FS\/18\/1\/33234"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/15\/30\/31390"],"award-info":[{"award-number":["PG\/15\/30\/31390"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human abdominal aortic aneurysms (AAAs) are characterized by increased activity of matrix metalloproteinases (MMP), including MMP-12, alongside macrophage accumulation and elastin degradation, in conjunction with superimposed atherosclerosis. Previous genetic ablation studies have proposed contradictory roles for MMP-12 in AAA development. In this study, we aimed to elucidate if pharmacological inhibition of MMP-12 activity with a phosphinic peptide inhibitor protects from AAA formation and progression in angiotensin (Ang) II-infused Apoe\u2212\/\u2212 mice. Complimentary studies were conducted in a human ex vivo model of early aneurysm development. Administration of an MMP-12 inhibitor (RXP470.1) protected hypercholesterolemia Apoe\u2212\/\u2212 mice from Ang II-induced AAA formation and rupture-related death, associated with diminished medial thinning and elastin fragmentation alongside increased collagen deposition. Proteomic analyses confirmed a beneficial effect of MMP-12 inhibition on extracellular matrix remodeling proteins combined with inflammatory pathways. Furthermore, RXP470.1 treatment of mice with pre-existing AAAs exerted beneficial effects as observed through suppressed aortic dilation and rupture, medial thinning, and elastin destruction. Our findings indicate that pharmacological inhibition of MMP-12 activity retards AAA progression and improves survival in mice providing proof-of-concept evidence to motivate translational work for MMP-12 inhibitor therapy in humans.<\/jats:p>","DOI":"10.3390\/ijms25115809","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T10:14:07Z","timestamp":1716804847000},"page":"5809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Pharmacological Inhibition of MMP-12 Exerts Protective Effects on Angiotensin II-Induced Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6152-369X","authenticated-orcid":false,"given":"Karina","family":"Di Gregoli","sequence":"first","affiliation":[{"name":"Laboratory of Cardiovascular Pathology, Department of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3454-7034","authenticated-orcid":false,"given":"Georgia","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pathology, Department of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Williams","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pathology, Department of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"George","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pathology, Department of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0630-9183","authenticated-orcid":false,"given":"Jason L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pathology, Department of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1161\/ATVBAHA.110.206573","article-title":"Atherosclerosis and abdominal aortic aneurysm","volume":"30","author":"Golledge","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nrcardio.2010.180","article-title":"Pathophysiology and epidemiology of abdominal aortic aneurysms","volume":"8","author":"Nordon","year":"2011","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/nrcardio.2009.80","article-title":"Biomarkers of aaa progression. Part 1: Extracellular matrix degeneration","volume":"6","author":"Hellenthal","year":"2009","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.jtcvs.2009.07.075","article-title":"Smooth muscle phenotypic modulation is an early event in aortic aneurysms","volume":"138","author":"Ailawadi","year":"2009","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nrcardio.2009.102","article-title":"Biomarkers of abdominal aortic aneurysm progression. Part 2: Inflammation","volume":"6","author":"Hellenthal","year":"2009","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/bjs.9838","article-title":"Age-specific incidence, risk factors and outcome of acute abdominal aortic aneurysms in a defined population","volume":"102","author":"Howard","year":"2015","journal-title":"Br. J. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1161\/CIRCULATIONAHA.108.802074","article-title":"Circulating markers of abdominal aortic aneurysm presence and progression","volume":"118","author":"Golledge","year":"2008","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.atherosclerosis.2017.10.017","article-title":"Lipoprotein(a) and abdominal aortic aneurysm risk: The atherosclerosis risk in communities study","volume":"268","author":"Kubota","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1126\/science.1142447","article-title":"A common allele on chromosome 9 associated with coronary heart disease","volume":"316","author":"McPherson","year":"2007","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/ejhg.2008.196","article-title":"Sequence variant on 9p21 is associated with the presence of abdominal aortic aneurysm disease but does not have an impact on aneurysmal expansion","volume":"17","author":"Thompson","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1161\/01.CIR.98.3.193","article-title":"Aortic aneurysm formation. Lessons from human studies and experimental models","volume":"98","author":"Davies","year":"1998","journal-title":"Circulation"},{"key":"ref_12","first-page":"e37","article-title":"Aortic aneurysms and dissections series","volume":"40","author":"Shen","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/cvr\/cvq337","article-title":"Novel aspects of the pathogenesis of aneurysms of the abdominal aorta in humans","volume":"90","author":"Michel","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1161\/01.ATV.0000214999.12921.4f","article-title":"Inflammation and cellular immune responses in abdominal aortic aneurysms","volume":"26","author":"Shimizu","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1248561","DOI":"10.3389\/fcvm.2023.1248561","article-title":"The contribution of matrix metalloproteinases and their inhibitors to the development, progression, and rupture of abdominal aortic aneurysms","volume":"10","author":"Atkinson","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_16","first-page":"21","article-title":"Matrix metalloproteinases and their inhibitors in cardiovascular pathologies: Current knowledge and clinical potential","volume":"1","author":"Johnson","year":"2014","journal-title":"Met. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15575","DOI":"10.1073\/pnas.0506201102","article-title":"Divergent effects of matrix metalloproteinases \u22123, \u22127, \u22129 and \u221212 on atherosclerotic plaque stability in mouse brachiocephalic arteries","volume":"102","author":"Johnson","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1161\/CIRCULATIONAHA.106.613281","article-title":"Suppression of atherosclerotic plaque progression and instability by tissue inhibitor of metalloproteinase-2: Involvement of macrophage migration and apoptosis","volume":"113","author":"Johnson","year":"2006","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1093\/cvr\/cvv268","article-title":"Differential effects of tissue inhibitor of metalloproteinase (timp)-1 and timp-2 on atherosclerosis and monocyte\/macrophage invasion","volume":"109","author":"George","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3942","DOI":"10.1073\/pnas.93.9.3942","article-title":"Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice","volume":"93","author":"Shipley","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1161\/ATVBAHA.110.219147","article-title":"A selective matrix metalloproteinase-12 inhibitor retards atherosclerotic plaque development in apolipoprotein e-knockout mice","volume":"31","author":"Johnson","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.avsg.2010.09.004","article-title":"Genes and abdominal aortic aneurysm","volume":"25","author":"Hinterseher","year":"2011","journal-title":"Ann. Vasc. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1038\/s41588-023-01510-y","article-title":"Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights pcsk9 as a therapeutic target","volume":"55","author":"Roychowdhury","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1172\/JCI2182","article-title":"Expression and localization of macrophage elastase (matrix metalloproteinase-12) in abdominal aortic aneurysms","volume":"102","author":"Curci","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1161\/ATVBAHA.120.314252","article-title":"Galectin-3 identifies a subset of macrophages with a potential beneficial role in atherosclerosis","volume":"40","author":"Somerville","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.surg.2004.12.004","article-title":"Mmp-12 has a role in abdominal aortic aneurysms in mice","volume":"137","author":"Longo","year":"2005","journal-title":"Surgery"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1172\/JCI8931","article-title":"Targeted gene disruption of matrix metalloproteinase-9 (gelatinase b) suppresses development of experimental abdominal aortic aneurysms","volume":"105","author":"Pyo","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1172\/JCI38136","article-title":"Tgf-b activity protects against inflammatory aortic aneurysm progression and complications in angiotensin ii-infused mice","volume":"120","author":"Wang","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1161\/CIRCRESAHA.122.322096","article-title":"Homeostatic, non-canonical role of macrophage elastase in vascular integrity","volume":"132","author":"Salarian","year":"2023","journal-title":"Circ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ejphar.2017.09.007","article-title":"Metalloproteinases in atherosclerosis","volume":"816","author":"Johnson","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1161\/01.CIR.0000121728.14930.DE","article-title":"Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein e-deficient mice against atherosclerotic media destruction but differentially affects plaque growth","volume":"109","author":"Luttun","year":"2004","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.avsg.2006.11.001","article-title":"Role of matrix metalloproteinase inhibitors in preventing abdominal aortic aneurysm","volume":"21","author":"Aziz","year":"2007","journal-title":"Ann. Vasc. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1126\/science.277.5334.2002","article-title":"Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice","volume":"277","author":"Hautamaki","year":"1997","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1161\/CIRCRESAHA.123.322511","article-title":"Divergent roles of matrix metalloproteinase 12 in abdominal aortic aneurysms","volume":"132","author":"Sawada","year":"2023","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Chen, Y., Yang, X., Kitajima, S., Quan, L., Wang, Y., Zhu, M., Liu, E., Lai, L., Yan, H., and Fan, J. (2023). Macrophage elastase derived from adventitial macrophages modulates aortic remodeling. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1097137"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1161\/CIRCULATIONAHA.107.745091","article-title":"Combined Inhibition of CCL2, CX3CR1, and CCR5 Abrogates Ly6Chi and Ly6Clo Monocytosis and Almost Abolishes Atherosclerosis in Hypercholesterolemic Mice","volume":"117","author":"Combadiere","year":"2008","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1161\/ATVBAHA.114.304389","article-title":"Angiotensin ii mobilizes spleen monocytes to promote the development of abdominal aortic aneurysm in apoe\u2212\/\u2212 mice","volume":"35","author":"Mellak","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1161\/01.RES.0000061571.49375.E1","article-title":"Urokinase-type plasminogen activator plays a critical role in angiotensin ii\u2013induced abdominal aortic aneurysm","volume":"92","author":"Deng","year":"2003","journal-title":"Circ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1093\/cvr\/cvy006","article-title":"From genetics to response to injury: Vascular smooth muscle cells in aneurysms and dissections of the ascending aorta","volume":"114","author":"Michel","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/cvr\/cvu257","article-title":"Dissecting abdominal aortic aneurysm in ang ii-infused mice: Suprarenal branch ruptures and apparent luminal dilatation","volume":"105","author":"Trachet","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1161\/ATVBAHA.116.307211","article-title":"Ascending aortic aneurysm in angiotensin ii\u2013infused mice: Formation, progression, and the role of focal dissections","volume":"36","author":"Trachet","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1161\/01.ATV.0000085631.76095.64","article-title":"Aortic dissection precedes formation of aneurysms and atherosclerosis in angiotensin ii-infused, apolipoprotein e-deficient mice","volume":"23","author":"Saraff","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1172\/JCI7818","article-title":"Angiotensin ii promotes atherosclerotic lesions and aneurysms in apolipoprotein e deficient mice","volume":"105","author":"Daugherty","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jss.2004.07.247","article-title":"Enhanced abdominal aortic aneurysm in timp-1-deficient mice","volume":"123","author":"Eskandari","year":"2005","journal-title":"J. Surg. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1172\/JCI2909","article-title":"Local overexpression of timp-1 prevents aortic aneurysm degeneration and rupture in a rat model","volume":"102","author":"Allaire","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.jvs.2006.06.036","article-title":"Effects of tissue inhibitor of metalloproteinase 2 deficiency on aneurysm formation","volume":"44","author":"Xiong","year":"2006","journal-title":"J. Vasc. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1161\/CIRCRESAHA.116.309321","article-title":"Microrna-181b controls atherosclerosis and aneurysms through regulation of timp-3 and elastin","volume":"120","author":"Bianco","year":"2017","journal-title":"Circ. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"44083","DOI":"10.1074\/jbc.M112.425652","article-title":"Loss of timp3 gene leads to abdominal aortic aneurysm formation in response to angiotensin II","volume":"287","author":"Basu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1161\/ATVBAHA.115.305631","article-title":"Elevated plasma levels of mmp-12 are associated with atherosclerotic burden and symptomatic cardiovascular disease in subjects with type 2 diabetes","volume":"35","author":"Goncalves","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Tanner, R.M., Lynch, A.I., Brophy, V.H., Eckfeldt, J.H., Davis, B.R., Ford, C.E., Boerwinkle, E., and Arnett, D.K. (2011). Pharmacogenetic associations of mmp9 and mmp12 variants with cardiovascular disease in patients with hypertension. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023609"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.amjcard.2007.01.069","article-title":"Plasma metalloproteinase-12 and tissue inhibitor of metalloproteinase-1 levels and presence, severity, and outcome of coronary artery disease","volume":"100","author":"Jelassi","year":"2007","journal-title":"Am. J. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.atherosclerosis.2008.03.020","article-title":"Inhibition of development of experimental aortic abdominal aneurysm in rat model by atorvastatin through inhibition of macrophage migration","volume":"202","author":"Shiraya","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ryter, S.W. (2022). Heme oxygenase-1: An anti-inflammatory effector in cardiovascular, lung, and related metabolic disorders. Antioxidants, 11.","DOI":"10.3390\/antiox11030555"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1089\/ars.2013.5184","article-title":"Interplay between heme oxygenase-1 and mir-378 affects non-small cell lung carcinoma growth, vascularization, and metastasis","volume":"19","author":"Skrzypek","year":"2013","journal-title":"Antioxid. Redox Signal"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"67760","DOI":"10.18632\/oncotarget.11917","article-title":"Heme oxygenase-1 deficiency exacerbates angiotensin ii-induced aortic aneurysm in mice","volume":"7","author":"Ho","year":"2016","journal-title":"Oncotarget"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kopacz, A., Kl\u00f3ska, D., Werner, E., Hajduk, K., Grochot-Prz\u0119czek, A., J\u00f3zkowicz, A., and Piechota-Pola\u0144czyk, A. (2021). A dual role of heme oxygenase-1 in angiotensin ii-induced abdominal aortic aneurysm in the normolipidemic mice. Cells, 10.","DOI":"10.3390\/cells10010163"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kilkenny, C., Browne, W.J., Cuthill, I.C., Emerson, M., and Altman, D.G. (2010). Improving bioscience research reporting: The arrive guidelines for reporting animal research. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000412"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1042\/CS20090372","article-title":"Angiotensin ii infusion promotes ascending aortic aneurysms: Attenuation by CCR2 deficiency in apoe\u2212\/\u2212 mice","volume":"118","author":"Daugherty","year":"2010","journal-title":"Clin. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jprot.2018.03.022","article-title":"The cardiac proteome in patients with congenital ventricular septal defect: A comparative study between right atria and right ventricles","volume":"191","author":"Bond","year":"2019","journal-title":"J. Proteom."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/11\/5809\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:49:13Z","timestamp":1760107753000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/11\/5809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,27]]},"references-count":59,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["ijms25115809"],"URL":"https:\/\/doi.org\/10.3390\/ijms25115809","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,27]]}}}