Systems Approach to Study Associations between OxLDL and Abdominal Aortic Aneurysms
Although abdominal aortic aneurysm (AAA) is a common vascular disease and is associated with high mortality, the full pathogenesis of AAA remains unknown to researchers. Abdominal aortic aneurysms and atherosclerosis are strongly related. Currently, it is more often suggested that development of AAA...
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| Veröffentlicht in: | International journal of molecular sciences 2019-08, Vol.20 (16), p.3909 |
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| description | Although abdominal aortic aneurysm (AAA) is a common vascular disease and is associated with high mortality, the full pathogenesis of AAA remains unknown to researchers. Abdominal aortic aneurysms and atherosclerosis are strongly related. Currently, it is more often suggested that development of AAA is not a result of atherosclerosis, however, individual factors can act independently or synergistically with atherosclerosis. One of such factors is low-density lipoprotein (LDL) and its oxidized form (oxLDL). It is known that oxLDL plays an important role in the pathogenesis of atherosclerosis, thus, we decided to examine oxLDL impact on the development of AAA by creating two models using Petri-nets. The first, full model, contains subprocess of LDL oxidation and all subprocesses in which it participates, while the second, reduced model, does not contain them. The analysis of such models can be based on
-invariants. They correspond to subprocesses which do not change the state of the modeled system. Moreover, the knockout analysis has been used to estimate how crucial a selected transition (representing elementary subprocess) is, based on the number of excluded subprocesses as a result of its knockout. The results of the analysis of our models show that oxLDL affects 55.84% of subprocesses related to AAA development, but the analysis of the nets based on knockouts and simulation has shown that the influence of oxLDL on enlargement and rupture of AAA is negligible. |
| doi_str_mv | 10.3390/ijms20163909 |
| format | Article |
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-invariants. They correspond to subprocesses which do not change the state of the modeled system. Moreover, the knockout analysis has been used to estimate how crucial a selected transition (representing elementary subprocess) is, based on the number of excluded subprocesses as a result of its knockout. The results of the analysis of our models show that oxLDL affects 55.84% of subprocesses related to AAA development, but the analysis of the nets based on knockouts and simulation has shown that the influence of oxLDL on enlargement and rupture of AAA is negligible.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20163909</identifier><identifier>PMID: 31405245</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Abdomen ; Activator protein 1 ; AKT protein ; Algorithms ; Aneurysms ; Animal models ; Animals ; Aorta ; Aortic Aneurysm, Abdominal - metabolism ; Aortic Aneurysm, Abdominal - pathology ; Aortic aneurysms ; Apoptosis ; Atherosclerosis ; Atherosclerosis - metabolism ; Atherosclerosis - pathology ; Cell adhesion & migration ; Chemokines ; Collagen ; Cytokines ; Disease Models, Animal ; Enzymes ; Humans ; Inflammation ; Lipoproteins, LDL - metabolism ; MAP kinase ; Models, Biological ; Muscles ; NAD(P)H oxidase ; Nitric oxide ; Nitric-oxide synthase ; Oxidative stress ; Pathogenesis ; Smooth muscle ; Transcription factors ; Tumor necrosis factor-TNF</subject><ispartof>International journal of molecular sciences, 2019-08, Vol.20 (16), p.3909</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-c106dd0636a78a4c135f200263089f493b472870eadbcc08a9d570112173b8493</citedby><cites>FETCH-LOGICAL-c412t-c106dd0636a78a4c135f200263089f493b472870eadbcc08a9d570112173b8493</cites><orcidid>0000-0001-6691-3863 ; 0000-0003-1221-4738 ; 0000-0002-5733-8809 ; 0000-0003-2719-3677 ; 0000-0002-5369-366X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721018/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721018/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31405245$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gutowski, Łukasz</creatorcontrib><creatorcontrib>Gutowska, Kaja</creatorcontrib><creatorcontrib>Pioruńska-Stolzmann, Maria</creatorcontrib><creatorcontrib>Formanowicz, Piotr</creatorcontrib><creatorcontrib>Formanowicz, Dorota</creatorcontrib><title>Systems Approach to Study Associations between OxLDL and Abdominal Aortic Aneurysms</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Although abdominal aortic aneurysm (AAA) is a common vascular disease and is associated with high mortality, the full pathogenesis of AAA remains unknown to researchers. Abdominal aortic aneurysms and atherosclerosis are strongly related. Currently, it is more often suggested that development of AAA is not a result of atherosclerosis, however, individual factors can act independently or synergistically with atherosclerosis. One of such factors is low-density lipoprotein (LDL) and its oxidized form (oxLDL). It is known that oxLDL plays an important role in the pathogenesis of atherosclerosis, thus, we decided to examine oxLDL impact on the development of AAA by creating two models using Petri-nets. The first, full model, contains subprocess of LDL oxidation and all subprocesses in which it participates, while the second, reduced model, does not contain them. The analysis of such models can be based on
-invariants. They correspond to subprocesses which do not change the state of the modeled system. Moreover, the knockout analysis has been used to estimate how crucial a selected transition (representing elementary subprocess) is, based on the number of excluded subprocesses as a result of its knockout. The results of the analysis of our models show that oxLDL affects 55.84% of subprocesses related to AAA development, but the analysis of the nets based on knockouts and simulation has shown that the influence of oxLDL on enlargement and rupture of AAA is negligible.</description><subject>Abdomen</subject><subject>Activator protein 1</subject><subject>AKT protein</subject><subject>Algorithms</subject><subject>Aneurysms</subject><subject>Animal models</subject><subject>Animals</subject><subject>Aorta</subject><subject>Aortic Aneurysm, Abdominal - metabolism</subject><subject>Aortic Aneurysm, Abdominal - pathology</subject><subject>Aortic aneurysms</subject><subject>Apoptosis</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - pathology</subject><subject>Cell adhesion & migration</subject><subject>Chemokines</subject><subject>Collagen</subject><subject>Cytokines</subject><subject>Disease Models, Animal</subject><subject>Enzymes</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Lipoproteins, LDL - metabolism</subject><subject>MAP kinase</subject><subject>Models, Biological</subject><subject>Muscles</subject><subject>NAD(P)H oxidase</subject><subject>Nitric oxide</subject><subject>Nitric-oxide synthase</subject><subject>Oxidative stress</subject><subject>Pathogenesis</subject><subject>Smooth muscle</subject><subject>Transcription factors</subject><subject>Tumor necrosis factor-TNF</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUtLAzEUhYMotlZ3riXgxoXVvCaZ2QiDbyi4qK5DJpPalJlJTTJq_72RVqmu7oXzcbjnHgCOMbqgtECXdtEGgjBPe7EDhpgRMkaIi92tfQAOQlggRCjJin0woJihjLBsCKbTVYimDbBcLr1Teg6jg9PY1ytYhuC0VdG6LsDKxA9jOvj0ObmZQNXVsKxq19pONbB0PloNy870fhXacAj2ZqoJ5mgzR-Dl7vb5-mE8ebp_vC4nY80wiWONEa9rxClXIldMY5rNSLqRU5QXM1bQigmSC2RUXWmNclXUmUAYEyxolSd9BK7Wvsu-ak2tTRe9auTS21b5lXTKyr9KZ-fy1b1LLghGOE8GZxsD7956E6JsbdCmaVRnXB8kIYIIyjPOEnr6D1243qf0iaIsAemdOFHna0p7F4I3s99jMJLfbcntthJ-sh3gF_6ph34Bq8CPew</recordid><startdate>20190811</startdate><enddate>20190811</enddate><creator>Gutowski, Łukasz</creator><creator>Gutowska, Kaja</creator><creator>Pioruńska-Stolzmann, Maria</creator><creator>Formanowicz, Piotr</creator><creator>Formanowicz, Dorota</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6691-3863</orcidid><orcidid>https://orcid.org/0000-0003-1221-4738</orcidid><orcidid>https://orcid.org/0000-0002-5733-8809</orcidid><orcidid>https://orcid.org/0000-0003-2719-3677</orcidid><orcidid>https://orcid.org/0000-0002-5369-366X</orcidid></search><sort><creationdate>20190811</creationdate><title>Systems Approach to Study Associations between OxLDL and Abdominal Aortic Aneurysms</title><author>Gutowski, Łukasz ; 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Abdominal aortic aneurysms and atherosclerosis are strongly related. Currently, it is more often suggested that development of AAA is not a result of atherosclerosis, however, individual factors can act independently or synergistically with atherosclerosis. One of such factors is low-density lipoprotein (LDL) and its oxidized form (oxLDL). It is known that oxLDL plays an important role in the pathogenesis of atherosclerosis, thus, we decided to examine oxLDL impact on the development of AAA by creating two models using Petri-nets. The first, full model, contains subprocess of LDL oxidation and all subprocesses in which it participates, while the second, reduced model, does not contain them. The analysis of such models can be based on
-invariants. They correspond to subprocesses which do not change the state of the modeled system. Moreover, the knockout analysis has been used to estimate how crucial a selected transition (representing elementary subprocess) is, based on the number of excluded subprocesses as a result of its knockout. The results of the analysis of our models show that oxLDL affects 55.84% of subprocesses related to AAA development, but the analysis of the nets based on knockouts and simulation has shown that the influence of oxLDL on enlargement and rupture of AAA is negligible.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31405245</pmid><doi>10.3390/ijms20163909</doi><orcidid>https://orcid.org/0000-0001-6691-3863</orcidid><orcidid>https://orcid.org/0000-0003-1221-4738</orcidid><orcidid>https://orcid.org/0000-0002-5733-8809</orcidid><orcidid>https://orcid.org/0000-0003-2719-3677</orcidid><orcidid>https://orcid.org/0000-0002-5369-366X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Abdomen Activator protein 1 AKT protein Algorithms Aneurysms Animal models Animals Aorta Aortic Aneurysm, Abdominal - metabolism Aortic Aneurysm, Abdominal - pathology Aortic aneurysms Apoptosis Atherosclerosis Atherosclerosis - metabolism Atherosclerosis - pathology Cell adhesion & migration Chemokines Collagen Cytokines Disease Models, Animal Enzymes Humans Inflammation Lipoproteins, LDL - metabolism MAP kinase Models, Biological Muscles NAD(P)H oxidase Nitric oxide Nitric-oxide synthase Oxidative stress Pathogenesis Smooth muscle Transcription factors Tumor necrosis factor-TNF |
| title | Systems Approach to Study Associations between OxLDL and Abdominal Aortic Aneurysms |
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