{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:16Z","timestamp":1787027716412,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T00:00:00Z","timestamp":1688428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Interdisciplinary Center for Clinical Research (IZKF) W\u00fcrzburg","award":["Z3_25"],"award-info":[{"award-number":["Z3_25"]}]},{"name":"Interdisciplinary Center for Clinical Research (IZKF) W\u00fcrzburg","award":["Z-6"],"award-info":[{"award-number":["Z-6"]}]},{"name":"Interdisciplinary Center for Clinical Research (IZKF) W\u00fcrzburg","award":["101088370"],"award-info":[{"award-number":["101088370"]}]},{"name":"Interdisciplinary Center for Clinical Research (IZKF) W\u00fcrzburg","award":["SFB1123"],"award-info":[{"award-number":["SFB1123"]}]},{"name":"Interdisciplinary Center for Clinical Research (IZKF) W\u00fcrzburg","award":["TRR267"],"award-info":[{"award-number":["TRR267"]}]},{"name":"Interdisciplinary Center for Clinical Research (IZKF) W\u00fcrzburg","award":["2019-01577"],"award-info":[{"award-number":["2019-01577"]}]},{"name":"Interdisciplinary Center for Clinical Research (IZKF) W\u00fcrzburg","award":["20210450"],"award-info":[{"award-number":["20210450"]}]},{"name":"German Vascular Society (DGG)","award":["Z3_25"],"award-info":[{"award-number":["Z3_25"]}]},{"name":"German Vascular Society (DGG)","award":["Z-6"],"award-info":[{"award-number":["Z-6"]}]},{"name":"German Vascular Society (DGG)","award":["101088370"],"award-info":[{"award-number":["101088370"]}]},{"name":"German Vascular Society (DGG)","award":["SFB1123"],"award-info":[{"award-number":["SFB1123"]}]},{"name":"German Vascular Society (DGG)","award":["TRR267"],"award-info":[{"award-number":["TRR267"]}]},{"name":"German Vascular Society (DGG)","award":["2019-01577"],"award-info":[{"award-number":["2019-01577"]}]},{"name":"German Vascular Society (DGG)","award":["20210450"],"award-info":[{"award-number":["20210450"]}]},{"name":"German Research Foundation (DFG)","award":["Z3_25"],"award-info":[{"award-number":["Z3_25"]}]},{"name":"German Research Foundation (DFG)","award":["Z-6"],"award-info":[{"award-number":["Z-6"]}]},{"name":"German Research Foundation (DFG)","award":["101088370"],"award-info":[{"award-number":["101088370"]}]},{"name":"German Research Foundation (DFG)","award":["SFB1123"],"award-info":[{"award-number":["SFB1123"]}]},{"name":"German Research Foundation (DFG)","award":["TRR267"],"award-info":[{"award-number":["TRR267"]}]},{"name":"German Research Foundation (DFG)","award":["2019-01577"],"award-info":[{"award-number":["2019-01577"]}]},{"name":"German Research Foundation (DFG)","award":["20210450"],"award-info":[{"award-number":["20210450"]}]},{"name":"IZKF W\u00fcrzburg","award":["Z3_25"],"award-info":[{"award-number":["Z3_25"]}]},{"name":"IZKF W\u00fcrzburg","award":["Z-6"],"award-info":[{"award-number":["Z-6"]}]},{"name":"IZKF W\u00fcrzburg","award":["101088370"],"award-info":[{"award-number":["101088370"]}]},{"name":"IZKF W\u00fcrzburg","award":["SFB1123"],"award-info":[{"award-number":["SFB1123"]}]},{"name":"IZKF W\u00fcrzburg","award":["TRR267"],"award-info":[{"award-number":["TRR267"]}]},{"name":"IZKF W\u00fcrzburg","award":["2019-01577"],"award-info":[{"award-number":["2019-01577"]}]},{"name":"IZKF W\u00fcrzburg","award":["20210450"],"award-info":[{"award-number":["20210450"]}]},{"name":"European Research Council","award":["Z3_25"],"award-info":[{"award-number":["Z3_25"]}]},{"name":"European Research Council","award":["Z-6"],"award-info":[{"award-number":["Z-6"]}]},{"name":"European Research Council","award":["101088370"],"award-info":[{"award-number":["101088370"]}]},{"name":"European Research Council","award":["SFB1123"],"award-info":[{"award-number":["SFB1123"]}]},{"name":"European Research Council","award":["TRR267"],"award-info":[{"award-number":["TRR267"]}]},{"name":"European Research Council","award":["2019-01577"],"award-info":[{"award-number":["2019-01577"]}]},{"name":"European Research Council","award":["20210450"],"award-info":[{"award-number":["20210450"]}]},{"name":"DZHK Translational Research Project (TRP)","award":["Z3_25"],"award-info":[{"award-number":["Z3_25"]}]},{"name":"DZHK Translational Research Project (TRP)","award":["Z-6"],"award-info":[{"award-number":["Z-6"]}]},{"name":"DZHK Translational Research Project (TRP)","award":["101088370"],"award-info":[{"award-number":["101088370"]}]},{"name":"DZHK Translational Research Project (TRP)","award":["SFB1123"],"award-info":[{"award-number":["SFB1123"]}]},{"name":"DZHK Translational Research Project (TRP)","award":["TRR267"],"award-info":[{"award-number":["TRR267"]}]},{"name":"DZHK Translational Research Project (TRP)","award":["2019-01577"],"award-info":[{"award-number":["2019-01577"]}]},{"name":"DZHK Translational Research Project (TRP)","award":["20210450"],"award-info":[{"award-number":["20210450"]}]},{"name":"German Research Council (DFG)","award":["Z3_25"],"award-info":[{"award-number":["Z3_25"]}]},{"name":"German Research Council (DFG)","award":["Z-6"],"award-info":[{"award-number":["Z-6"]}]},{"name":"German Research Council (DFG)","award":["101088370"],"award-info":[{"award-number":["101088370"]}]},{"name":"German Research Council (DFG)","award":["SFB1123"],"award-info":[{"award-number":["SFB1123"]}]},{"name":"German Research Council (DFG)","award":["TRR267"],"award-info":[{"award-number":["TRR267"]}]},{"name":"German Research Council (DFG)","award":["2019-01577"],"award-info":[{"award-number":["2019-01577"]}]},{"name":"German Research Council (DFG)","award":["20210450"],"award-info":[{"award-number":["20210450"]}]},{"name":"Vetenkapsr\u00e5det","award":["Z3_25"],"award-info":[{"award-number":["Z3_25"]}]},{"name":"Vetenkapsr\u00e5det","award":["Z-6"],"award-info":[{"award-number":["Z-6"]}]},{"name":"Vetenkapsr\u00e5det","award":["101088370"],"award-info":[{"award-number":["101088370"]}]},{"name":"Vetenkapsr\u00e5det","award":["SFB1123"],"award-info":[{"award-number":["SFB1123"]}]},{"name":"Vetenkapsr\u00e5det","award":["TRR267"],"award-info":[{"award-number":["TRR267"]}]},{"name":"Vetenkapsr\u00e5det","award":["2019-01577"],"award-info":[{"award-number":["2019-01577"]}]},{"name":"Vetenkapsr\u00e5det","award":["20210450"],"award-info":[{"award-number":["20210450"]}]},{"name":"Hj\u00e4rt-Lungfonden","award":["Z3_25"],"award-info":[{"award-number":["Z3_25"]}]},{"name":"Hj\u00e4rt-Lungfonden","award":["Z-6"],"award-info":[{"award-number":["Z-6"]}]},{"name":"Hj\u00e4rt-Lungfonden","award":["101088370"],"award-info":[{"award-number":["101088370"]}]},{"name":"Hj\u00e4rt-Lungfonden","award":["SFB1123"],"award-info":[{"award-number":["SFB1123"]}]},{"name":"Hj\u00e4rt-Lungfonden","award":["TRR267"],"award-info":[{"award-number":["TRR267"]}]},{"name":"Hj\u00e4rt-Lungfonden","award":["2019-01577"],"award-info":[{"award-number":["2019-01577"]}]},{"name":"Hj\u00e4rt-Lungfonden","award":["20210450"],"award-info":[{"award-number":["20210450"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Popliteal artery aneurysm (PAA) is the most frequent peripheral aneurysm, primarily seen in male smokers with a prevalence below 1%. This exploratory study aims to shed light on cellular mechanisms involved in PAA progression. Sixteen human PAA and eight non-aneurysmatic popliteal artery samples, partially from the same patients, were analyzed by immunohistochemistry, fluorescence imaging, Affymetrix mRNA expression profiling, qPCR and OLink proteomics, and compared to atherosclerotic (n = 6) and abdominal aortic aneurysm (AAA) tissue (n = 19). Additionally, primary cell culture of PAA-derived vascular smooth muscle cells (VSMC) was established for modulation and growth analysis. Compared to non-aneurysmatic popliteal arteries, VSMCs lose the contractile phenotype and the cell proliferation rate increases significantly in PAA. Array analysis identified APOE higher expressed in PAA samples, co-localizing with VSMCs. APOE stimulation of primary human PAA VSMCs significantly reduced cell proliferation. Accordingly, contractile VSMC markers were significantly upregulated. A single case of osseous mechanically induced PAA with a non-diseased VSMC profile emphasizes these findings. Carefully concluded, PAA pathogenesis shows similar features to AAA, yet the mechanisms involved might differ. APOE is specifically higher expressed in PAA tissue and could be involved in VSMC phenotype rescue.<\/jats:p>","DOI":"10.3390\/biom13071074","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:33:42Z","timestamp":1688517222000},"page":"1074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Apolipoprotein E (ApoE) Rescues the Contractile Smooth Muscle Cell Phenotype in Popliteal Artery Aneurysm Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5984-3529","authenticated-orcid":false,"given":"Jessica","family":"Pauli","sequence":"first","affiliation":[{"name":"Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Reisenauer","sequence":"additional","affiliation":[{"name":"Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1832-5423","authenticated-orcid":false,"given":"Greg","family":"Winski","sequence":"additional","affiliation":[{"name":"Molecular Vascular Medicine Group, Center for Molecular Medicine, Karolinska Institute, 17177 Stockholm, Sweden"},{"name":"Perioperative Medicine and Intensive Care, Karolinska University Hospital, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8031-017X","authenticated-orcid":false,"given":"Nadja","family":"Sachs","sequence":"additional","affiliation":[{"name":"Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Chernogubova","sequence":"additional","affiliation":[{"name":"Molecular Vascular Medicine Group, Center for Molecular Medicine, Karolinska Institute, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Freytag","sequence":"additional","affiliation":[{"name":"Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplantation, Vascular & Pediatric Surgery, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Reeps","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department for Visceral, Thoracic and Vascular Surgery, Medical Faculty Carl Gustav Carus and University Hospital, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Henning","family":"Eckstein","sequence":"additional","affiliation":[{"name":"Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6406-7859","authenticated-orcid":false,"given":"Claus-J\u00fcrgen","family":"Scholz","sequence":"additional","affiliation":[{"name":"Wisplinghoff Laboratories, 50858 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Maegdefessel","sequence":"additional","affiliation":[{"name":"Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 10785 Berlin, Germany"},{"name":"Molecular Vascular Medicine Group, Center for Molecular Medicine, Karolinska Institute, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2374-0338","authenticated-orcid":false,"given":"Albert","family":"Busch","sequence":"additional","affiliation":[{"name":"Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany"},{"name":"Division of Vascular and Endovascular Surgery, Department for Visceral, Thoracic and Vascular Surgery, Medical Faculty Carl Gustav Carus and University Hospital, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1136\/jms.9.2.92","article-title":"Screening and management of asymptomatic popliteal aneurysms","volume":"9","author":"Trickett","year":"2002","journal-title":"J. Med. Screen."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1177\/1358863X16648404","article-title":"Patients with abdominal aortic aneurysm have a high prevalence of popliteal artery aneurysms","volume":"21","author":"Tuveson","year":"2016","journal-title":"Vasc. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/bjs.6074","article-title":"Risk of new aneurysms after surgery for popliteal artery aneurysm","volume":"95","author":"Ravn","year":"2008","journal-title":"Br. J. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.ejvs.2011.02.007","article-title":"Part One: For the Motion: Asymptomatic Popliteal Artery Aneurysms (less than 3 cm) Should be Treated Conservatively","volume":"41","author":"Cross","year":"2011","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.jvs.2022.03.892","article-title":"Female sex portends increased risk of major amputation following surgical repair of symptomatic popliteal artery aneurysms","volume":"76","author":"Naazie","year":"2022","journal-title":"J. Vasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.ejvs.2020.07.005","article-title":"Contemporary Treatment of Popliteal Artery Aneurysms in 14 Countries: A Vascunet Report","volume":"60","author":"Grip","year":"2020","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.ejvs.2015.03.026","article-title":"Treatment of Popliteal Aneurysm by Open and Endovascular Surgery: A Contemporary Study of 592 Procedures in Sweden","volume":"50","author":"Cervin","year":"2015","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.jvs.2012.10.112","article-title":"Results of elective and emergency endovascular repairs of popliteal artery aneurysms","volume":"57","author":"Ricotta","year":"2013","journal-title":"J. Vasc. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"109S","DOI":"10.1016\/j.jvs.2021.04.040","article-title":"The Society for Vascular Surgery clinical practice guidelines on popliteal artery aneurysms","volume":"75","author":"Farber","year":"2021","journal-title":"J. Vasc. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1315.e7","DOI":"10.1016\/j.avsg.2015.02.020","article-title":"Exostoses and Vascular Complications in the Lower Limbs: Two Case Reports and Review of the Literature","volume":"29","author":"Nasr","year":"2015","journal-title":"Ann. Vasc. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1097\/00000478-198304000-00003","article-title":"Bizarre parosteal osteochondromatous proliferations of the hands and feet","volume":"7","author":"Nora","year":"1983","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.jvs.2012.01.064","article-title":"Bilateral popliteal artery aneurysms in a young man with Loeys-Dietz syndrome","volume":"56","author":"Stephenson","year":"2012","journal-title":"J. Vasc. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.ejvs.2011.05.010","article-title":"Surgical Treatment of Peripheral Aneurysms in Patients with Behcet\u2019s Disease","volume":"42","author":"Koksoy","year":"2011","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.jvs.2003.12.005","article-title":"The popliteal artery, an unusual muscular artery with wall properties similar to the aorta: Implications for susceptibility to aneurysm formation?","volume":"39","author":"Debasso","year":"2004","journal-title":"J. Vasc. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1177\/1358863X14524851","article-title":"Low wall stress in the popliteal artery: Other mechanisms responsible for the predilection of aneurysmal dilatation?","volume":"19","author":"Astrand","year":"2014","journal-title":"Vasc. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00418-017-1575-3","article-title":"Vessel wall morphology is equivalent for different artery types and localizations of advanced human aneurysms","volume":"148","author":"Busch","year":"2017","journal-title":"Histochem. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1016\/j.jvs.2010.01.057","article-title":"The pathophysiology of abdominal aortic aneurysm growth: Corresponding and discordant inflammatory and proteolytic processes in abdominal aortic and popliteal artery aneurysms","volume":"51","author":"Hanemaaijer","year":"2010","journal-title":"J. Vasc. Surg."},{"key":"ref_18","first-page":"e140364","article-title":"Lenvatinib halts aortic aneurysm growth by restoring smooth muscle cell contractility","volume":"6","author":"Busch","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11661","DOI":"10.1074\/jbc.M211337200","article-title":"Kruppel-like factor 4 (KLF4\/GKLF) is a target of bone morphogenetic proteins and transforming growth factor beta 1 in the regulation of vascular smooth muscle cell phenotype","volume":"278","author":"King","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000484088","article-title":"Progressive Development of Aberrant Smooth Muscle Cell Phenotype in Abdominal Aortic Aneurysm Disease","volume":"55","author":"Clark","year":"2018","journal-title":"J. Vasc. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.jtcvs.2011.07.053","article-title":"Bone marrow\u2013derived MCP1 required for experimental aortic aneurysm formation and smooth muscle phenotypic modulation","volume":"142","author":"Moehle","year":"2011","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0022-4804(03)00121-5","article-title":"Differential expression of YAMA\/CPP-32 by T lymphocytes in popliteal artery aneurysm","volume":"112","author":"Jacob","year":"2003","journal-title":"J. Surg. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.jvs.2014.08.088","article-title":"Popliteal artery aneurysms differ from abdominal aortic aneurysms in cellular topography and inflammatory markers","volume":"60","author":"Hurks","year":"2014","journal-title":"J. Vasc. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/j.jvs.2016.07.129","article-title":"Heterogeneous histomorphology, yet homogeneous vascular smooth muscle cell dedifferentiation, characterize human aneurysm disease","volume":"66","author":"Busch","year":"2017","journal-title":"J. Vasc. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pelisek, J., Hegenloh, R., Bauer, S., Metschl, S., Pauli, J., Glukha, N., Busch, A., Reutersberg, B., Kallmayer, M., and Trenner, M. (2019). Biobanking: Objectives, Requirements, and Future Challenges-Experiences from the Munich Vascular Biobank. J. Clin. Med., 8.","DOI":"10.3390\/jcm8020251"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Assarsson, E., Lundberg, M., Holmquist, G., Bj\u00f6rkesten, J., Thorsen, S.B., Ekman, D., Eriksson, A., Dickens, E.R., Ohlsson, S., and Edfeldt, G. (2014). Homogenous 96-Plex PEA Immunoassay Exhibiting High Sensitivity, Specificity, and Excellent Scalability. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095192"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.atherosclerosis.2015.07.023","article-title":"Use of a proximity extension assay proteomics chip to discover new biomarkers for human atherosclerosis","volume":"242","author":"Lind","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1093\/nar\/30.1.42","article-title":"The KEGG databases at GenomeNet","volume":"30","author":"Kanehisa","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Fabregat, A., Sidiropoulos, K., Viteri, G., Forner, O., Marin-Garcia, P., Arnau, V., D\u2019eustachio, P., Stein, L., and Hermjakob, H. (2017). Reactome pathway analysis: A high-performance in-memory approach. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1559-2"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sachdeva, J., Mahajan, A., Cheng, J., Baeten, J.T., Lilly, B., Kuivaniemi, H., and Hans, C.P. (2017). Smooth muscle cell-specific Notch1 haploinsufficiency restricts the progression of abdominal aortic aneurysm by modulating CTGF expression. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178538"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0950-821X(05)80118-5","article-title":"Inflammation of the abdominal aortic aneurysm wall","volume":"8","author":"Rijbroek","year":"1994","journal-title":"Eur. J. Vasc. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1002\/bjs.10955","article-title":"Modelling the growth of popliteal artery aneurysms","volume":"105","author":"Shiwani","year":"2018","journal-title":"Br. J. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jvssci.2021.04.003","article-title":"Circulating microRNA in patients with popliteal and multiple artery aneurysms","volume":"2","author":"Ravn","year":"2021","journal-title":"JVS Vasc. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Busch, A., Busch, M., Scholz, C.-J., Kellersmann, R., Otto, C., Chernogubova, E., Maegdefessel, L., Zernecke, A., and Lorenz, U. (2016). Aneurysm miRNA Signature Differs, Depending on Disease Localization and Morphology. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010081"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.surg.2014.06.008","article-title":"The role of matrix metalloproteinases and neutrophil gelatinase-associated lipocalin in central and peripheral arterial aneurysms","volume":"157","author":"Serra","year":"2015","journal-title":"Surgery"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/08998280.2012.11928880","article-title":"Nora\u2019s lesion: Bizarre parosteal osteochondromatous proliferation of the tibia","volume":"25","author":"Kershen","year":"2012","journal-title":"Proc. Bayl. Univ. Med. Cent."},{"key":"ref_40","first-page":"331","article-title":"Parietal inflammatory infiltrate in peripheral aneurysms of atherosclerotic origin","volume":"33","author":"Faggioli","year":"1992","journal-title":"J. Cardiovasc. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"698.e13","DOI":"10.1016\/j.avsg.2010.12.026","article-title":"Inflammatory Popliteal Aneurysm","volume":"25","author":"Akamatsu","year":"2011","journal-title":"Ann. Vasc. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jvssci.2021.01.002","article-title":"Translating mouse models of abdominal aortic aneurysm to the translational needs of vascular surgery","volume":"2","author":"Busch","year":"2021","journal-title":"JVS Vasc. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/acel.12362","article-title":"Genetic evidence for common pathways in human age-related diseases","volume":"14","author":"Johnson","year":"2015","journal-title":"Aging Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ejvs.2017.07.018","article-title":"Editor\u2019s Choice\u20142017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)","volume":"55","author":"Aboyans","year":"2018","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"877","DOI":"10.2147\/VHRM.S1866","article-title":"Prevalence of risk factors, coronary and systemic atherosclerosis in abdominal aortic aneurysm: Comparison with high cardiovascular risk population","volume":"4","author":"Palazzuoli","year":"2008","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1161\/CIRCRESAHA.115.306427","article-title":"Adaptive Response of T and B Cells in Atherosclerosis","volume":"118","author":"Ketelhuth","year":"2016","journal-title":"Circ. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41572-018-0030-7","article-title":"Abdominal aortic aneurysms","volume":"4","author":"Sakalihasan","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.jtcvs.2008.06.027","article-title":"Regional heterogeneity within the aorta: Relevance to aneurysm disease","volume":"136","author":"Ruddy","year":"2008","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/nature10145","article-title":"Lessons on the pathogenesis of aneurysm from heritable conditions","volume":"473","author":"Lindsay","year":"2011","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"C1393","DOI":"10.1152\/ajpcell.00046.2022","article-title":"Exploring the difference in the mechanics of vascular smooth muscle cells from wild-type and apolipoprotein-E knockout mice","volume":"323","author":"Rickel","year":"2022","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1093\/cvr\/cvs115","article-title":"Smooth muscle cell phenotypic switching in atherosclerosis","volume":"95","author":"Gomez","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Schwartz, S.M., Virmani, R., and Majesky, M.W. (2018). An update on clonality: What smooth muscle cell type makes up the atherosclerotic plaque?. F1000Research, 7.","DOI":"10.12688\/f1000research.15994.1"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1053\/ejvs.2001.1344","article-title":"Examination of the Apoptotic Pathway and Proteolysis in the Pathogenesis of Popliteal Artery Aneurysms","volume":"22","author":"Jacob","year":"2001","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1006\/jsre.2001.6193","article-title":"Initial Steps in the Unifying Theory of the Pathogenesis of Artery Aneurysms","volume":"101","author":"Jacob","year":"2001","journal-title":"J. Surg. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.ejvs.2007.12.004","article-title":"Elevated Plasma MMP1 and MMP9 are Associated with Abdominal Aortic Aneurysm Rupture","volume":"35","author":"Wilson","year":"2008","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1161\/ATVBAHA.119.312787","article-title":"Role of Vascular Smooth Muscle Cell Phenotypic Switching and Calcification in Aortic Aneurysm Formation","volume":"39","author":"Petsophonsakul","year":"2019","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1093\/cvr\/cvab088","article-title":"Organ-on-a-chip technology: A novel approach to investigate cardiovascular diseases","volume":"117","author":"Paloschi","year":"2021","journal-title":"Cardiovasc. Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/7\/1074\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:05:59Z","timestamp":1760126759000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/7\/1074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,4]]},"references-count":58,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["biom13071074"],"URL":"https:\/\/doi.org\/10.3390\/biom13071074","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,4]]}}}