Congestive heart failure in COX2 deficient rats

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin (PG) formation by targeting cyclooxygenase (COX) 1 and 2. Long-term use of NSAIDs that selectively inhibit COX2 increases the risk for thrombotic events, cardiac failure, and hypertension. However, the underlying mechanisms remain...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Science China. Life sciences 2021-07, Vol.64 (7), p.1068-1076
Hauptverfasser:	Wan, Qiangyou, Kong, Deping, Liu, Qian, Guo, Shumin, Wang, Chenchen, Zhao, Yan, Ke, Zun-Ji, Yu, Ying
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology Biomarkers - metabolism Biomedical and Life Sciences Congestive heart failure Cyclooxygenase 1 - metabolism Cyclooxygenase 2 - metabolism Cyclooxygenase 2 Inhibitors - pharmacology Cyclooxygenase-1 Cyclooxygenase-2 Echocardiography Energy Metabolism Fibrosis Gene targeting Genotype Genotyping Glycolysis Heart failure Heart Failure - diagnostic imaging Heart Failure - drug therapy Heart Failure - metabolism Hexokinase Inflammation Life Sciences Mitochondria Nonsteroidal anti-inflammatory drugs Oxidation Pyruvate dehydrogenase (lipoamide) Pyruvic acid Rats Rats, Sprague-Dawley Research Paper Stroke Volume Ventricle
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

container_end_page	1076
container_issue	7
container_start_page	1068
container_title	Science China. Life sciences
container_volume	64
creator	Wan, Qiangyou Kong, Deping Liu, Qian Guo, Shumin Wang, Chenchen Zhao, Yan Ke, Zun-Ji Yu, Ying
description	Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin (PG) formation by targeting cyclooxygenase (COX) 1 and 2. Long-term use of NSAIDs that selectively inhibit COX2 increases the risk for thrombotic events, cardiac failure, and hypertension. However, the underlying mechanisms remain unclear. In this study, COX1- and COX2-deficient rats were created via Cas9/RNA-mediated gene targeting. DNA genotyping and Western blot analysis confirmed successful generation of COX1 −/− and COX2 −/− rats. Adult COX1 −/− rats grew normally, while more than 70% of COX2 −/− rats after wean died within 2 months. Echocardiography showed markedly reduced left ventricular ejection fraction and fractional shortening in adult COX2 −/− rats compared to those in wildtype (WT) controls. Histological analysis revealed accumulation of inflammatory cells and severe interstitial and perivascular fibrosis in COX2 −/− cardiac tissues. Moreover, cardiac ATP and acetyl-CoA production was dramatically decreased in COX2 −/− rats. Consistently, the expression of genes related to mitochondrial oxidation, such as those that encode for subunits of pyruvate dehydrogenase complex and acyl CoA dehydrogenases, were downregulated, while glycolytic hexokinase 1 (HK1) was upregulated in COX2 −/− heart tissues. These observations indicate that COX2-deficient rats developed spontaneously heart failure, likely as a result of dysregulated cardiac energy metabolism.
doi_str_mv	10.1007/s11427-020-1792-5
format	Article
fullrecord	<record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2444608435</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2547980282</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-a04321cc6b37ede224db7db4b9baa623ecc009dc669254e43c4732877214f5083</originalsourceid><addsrcrecordid>eNp1kE1LwzAYgIMobsz9AC9S8OIlLnnz2aMMv2Cwi4K3kKapdnTtTFrBf29Gp4JgLgnkyZOXB6FzSq4pIWoRKeWgMAGCqcoBiyM0pVrmmGqdH6ezVBwrRsQEzWPckLQYI6DUKZowyIWQQk_RYtm1rz729YfP3rwNfVbZuhmCz-o2W65fICt9Vbvat30WbB_P0Ellm-jnh32Gnu9un5YPeLW-f1zerLBjCnpsCWdAnZMFU770ALwsVFnwIi-slcC8c4TkpZMyB8E9Z44rBlopoLwSRLMZuhq9u9C9D2lAs62j801jW98N0QDnXBLNmUjo5R900w2hTdOZ5Fa5JqAhUXSkXOhiDL4yu1Bvbfg0lJh9UDMGNSmo2Qc1e_PFwTwUW1_-vPjOlwAYgZiuUsfw-_X_1i9j2H0Y</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2547980282</pqid></control><display><type>article</type><title>Congestive heart failure in COX2 deficient rats</title><source>MEDLINE</source><source>SpringerNature Journals</source><source>Alma/SFX Local Collection</source><creator>Wan, Qiangyou ; Kong, Deping ; Liu, Qian ; Guo, Shumin ; Wang, Chenchen ; Zhao, Yan ; Ke, Zun-Ji ; Yu, Ying</creator><creatorcontrib>Wan, Qiangyou ; Kong, Deping ; Liu, Qian ; Guo, Shumin ; Wang, Chenchen ; Zhao, Yan ; Ke, Zun-Ji ; Yu, Ying</creatorcontrib><description>Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin (PG) formation by targeting cyclooxygenase (COX) 1 and 2. Long-term use of NSAIDs that selectively inhibit COX2 increases the risk for thrombotic events, cardiac failure, and hypertension. However, the underlying mechanisms remain unclear. In this study, COX1- and COX2-deficient rats were created via Cas9/RNA-mediated gene targeting. DNA genotyping and Western blot analysis confirmed successful generation of COX1 −/− and COX2 −/− rats. Adult COX1 −/− rats grew normally, while more than 70% of COX2 −/− rats after wean died within 2 months. Echocardiography showed markedly reduced left ventricular ejection fraction and fractional shortening in adult COX2 −/− rats compared to those in wildtype (WT) controls. Histological analysis revealed accumulation of inflammatory cells and severe interstitial and perivascular fibrosis in COX2 −/− cardiac tissues. Moreover, cardiac ATP and acetyl-CoA production was dramatically decreased in COX2 −/− rats. Consistently, the expression of genes related to mitochondrial oxidation, such as those that encode for subunits of pyruvate dehydrogenase complex and acyl CoA dehydrogenases, were downregulated, while glycolytic hexokinase 1 (HK1) was upregulated in COX2 −/− heart tissues. These observations indicate that COX2-deficient rats developed spontaneously heart failure, likely as a result of dysregulated cardiac energy metabolism.</description><identifier>ISSN: 1674-7305</identifier><identifier>EISSN: 1869-1889</identifier><identifier>DOI: 10.1007/s11427-020-1792-5</identifier><identifier>PMID: 32955658</identifier><language>eng</language><publisher>Beijing: Science China Press</publisher><subject>Animals ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Biomarkers - metabolism ; Biomedical and Life Sciences ; Congestive heart failure ; Cyclooxygenase 1 - metabolism ; Cyclooxygenase 2 - metabolism ; Cyclooxygenase 2 Inhibitors - pharmacology ; Cyclooxygenase-1 ; Cyclooxygenase-2 ; Echocardiography ; Energy Metabolism ; Fibrosis ; Gene targeting ; Genotype ; Genotyping ; Glycolysis ; Heart failure ; Heart Failure - diagnostic imaging ; Heart Failure - drug therapy ; Heart Failure - metabolism ; Hexokinase ; Inflammation ; Life Sciences ; Mitochondria ; Nonsteroidal anti-inflammatory drugs ; Oxidation ; Pyruvate dehydrogenase (lipoamide) ; Pyruvic acid ; Rats ; Rats, Sprague-Dawley ; Research Paper ; Stroke Volume ; Ventricle</subject><ispartof>Science China. Life sciences, 2021-07, Vol.64 (7), p.1068-1076</ispartof><rights>Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-a04321cc6b37ede224db7db4b9baa623ecc009dc669254e43c4732877214f5083</citedby><cites>FETCH-LOGICAL-c372t-a04321cc6b37ede224db7db4b9baa623ecc009dc669254e43c4732877214f5083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11427-020-1792-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11427-020-1792-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27926,27927,41490,42559,51321</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32955658$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wan, Qiangyou</creatorcontrib><creatorcontrib>Kong, Deping</creatorcontrib><creatorcontrib>Liu, Qian</creatorcontrib><creatorcontrib>Guo, Shumin</creatorcontrib><creatorcontrib>Wang, Chenchen</creatorcontrib><creatorcontrib>Zhao, Yan</creatorcontrib><creatorcontrib>Ke, Zun-Ji</creatorcontrib><creatorcontrib>Yu, Ying</creatorcontrib><title>Congestive heart failure in COX2 deficient rats</title><title>Science China. Life sciences</title><addtitle>Sci. China Life Sci</addtitle><addtitle>Sci China Life Sci</addtitle><description>Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin (PG) formation by targeting cyclooxygenase (COX) 1 and 2. Long-term use of NSAIDs that selectively inhibit COX2 increases the risk for thrombotic events, cardiac failure, and hypertension. However, the underlying mechanisms remain unclear. In this study, COX1- and COX2-deficient rats were created via Cas9/RNA-mediated gene targeting. DNA genotyping and Western blot analysis confirmed successful generation of COX1 −/− and COX2 −/− rats. Adult COX1 −/− rats grew normally, while more than 70% of COX2 −/− rats after wean died within 2 months. Echocardiography showed markedly reduced left ventricular ejection fraction and fractional shortening in adult COX2 −/− rats compared to those in wildtype (WT) controls. Histological analysis revealed accumulation of inflammatory cells and severe interstitial and perivascular fibrosis in COX2 −/− cardiac tissues. Moreover, cardiac ATP and acetyl-CoA production was dramatically decreased in COX2 −/− rats. Consistently, the expression of genes related to mitochondrial oxidation, such as those that encode for subunits of pyruvate dehydrogenase complex and acyl CoA dehydrogenases, were downregulated, while glycolytic hexokinase 1 (HK1) was upregulated in COX2 −/− heart tissues. These observations indicate that COX2-deficient rats developed spontaneously heart failure, likely as a result of dysregulated cardiac energy metabolism.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Biomarkers - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Congestive heart failure</subject><subject>Cyclooxygenase 1 - metabolism</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Cyclooxygenase 2 Inhibitors - pharmacology</subject><subject>Cyclooxygenase-1</subject><subject>Cyclooxygenase-2</subject><subject>Echocardiography</subject><subject>Energy Metabolism</subject><subject>Fibrosis</subject><subject>Gene targeting</subject><subject>Genotype</subject><subject>Genotyping</subject><subject>Glycolysis</subject><subject>Heart failure</subject><subject>Heart Failure - diagnostic imaging</subject><subject>Heart Failure - drug therapy</subject><subject>Heart Failure - metabolism</subject><subject>Hexokinase</subject><subject>Inflammation</subject><subject>Life Sciences</subject><subject>Mitochondria</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Oxidation</subject><subject>Pyruvate dehydrogenase (lipoamide)</subject><subject>Pyruvic acid</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Research Paper</subject><subject>Stroke Volume</subject><subject>Ventricle</subject><issn>1674-7305</issn><issn>1869-1889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1LwzAYgIMobsz9AC9S8OIlLnnz2aMMv2Cwi4K3kKapdnTtTFrBf29Gp4JgLgnkyZOXB6FzSq4pIWoRKeWgMAGCqcoBiyM0pVrmmGqdH6ezVBwrRsQEzWPckLQYI6DUKZowyIWQQk_RYtm1rz729YfP3rwNfVbZuhmCz-o2W65fICt9Vbvat30WbB_P0Ellm-jnh32Gnu9un5YPeLW-f1zerLBjCnpsCWdAnZMFU770ALwsVFnwIi-slcC8c4TkpZMyB8E9Z44rBlopoLwSRLMZuhq9u9C9D2lAs62j801jW98N0QDnXBLNmUjo5R900w2hTdOZ5Fa5JqAhUXSkXOhiDL4yu1Bvbfg0lJh9UDMGNSmo2Qc1e_PFwTwUW1_-vPjOlwAYgZiuUsfw-_X_1i9j2H0Y</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Wan, Qiangyou</creator><creator>Kong, Deping</creator><creator>Liu, Qian</creator><creator>Guo, Shumin</creator><creator>Wang, Chenchen</creator><creator>Zhao, Yan</creator><creator>Ke, Zun-Ji</creator><creator>Yu, Ying</creator><general>Science China Press</general><general>Springer Nature B.V</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>7QP</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20210701</creationdate><title>Congestive heart failure in COX2 deficient rats</title><author>Wan, Qiangyou ; Kong, Deping ; Liu, Qian ; Guo, Shumin ; Wang, Chenchen ; Zhao, Yan ; Ke, Zun-Ji ; Yu, Ying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-a04321cc6b37ede224db7db4b9baa623ecc009dc669254e43c4732877214f5083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Biomarkers - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Congestive heart failure</topic><topic>Cyclooxygenase 1 - metabolism</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Cyclooxygenase 2 Inhibitors - pharmacology</topic><topic>Cyclooxygenase-1</topic><topic>Cyclooxygenase-2</topic><topic>Echocardiography</topic><topic>Energy Metabolism</topic><topic>Fibrosis</topic><topic>Gene targeting</topic><topic>Genotype</topic><topic>Genotyping</topic><topic>Glycolysis</topic><topic>Heart failure</topic><topic>Heart Failure - diagnostic imaging</topic><topic>Heart Failure - drug therapy</topic><topic>Heart Failure - metabolism</topic><topic>Hexokinase</topic><topic>Inflammation</topic><topic>Life Sciences</topic><topic>Mitochondria</topic><topic>Nonsteroidal anti-inflammatory drugs</topic><topic>Oxidation</topic><topic>Pyruvate dehydrogenase (lipoamide)</topic><topic>Pyruvic acid</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Research Paper</topic><topic>Stroke Volume</topic><topic>Ventricle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wan, Qiangyou</creatorcontrib><creatorcontrib>Kong, Deping</creatorcontrib><creatorcontrib>Liu, Qian</creatorcontrib><creatorcontrib>Guo, Shumin</creatorcontrib><creatorcontrib>Wang, Chenchen</creatorcontrib><creatorcontrib>Zhao, Yan</creatorcontrib><creatorcontrib>Ke, Zun-Ji</creatorcontrib><creatorcontrib>Yu, Ying</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Science China. Life sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wan, Qiangyou</au><au>Kong, Deping</au><au>Liu, Qian</au><au>Guo, Shumin</au><au>Wang, Chenchen</au><au>Zhao, Yan</au><au>Ke, Zun-Ji</au><au>Yu, Ying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Congestive heart failure in COX2 deficient rats</atitle><jtitle>Science China. Life sciences</jtitle><stitle>Sci. China Life Sci</stitle><addtitle>Sci China Life Sci</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>64</volume><issue>7</issue><spage>1068</spage><epage>1076</epage><pages>1068-1076</pages><issn>1674-7305</issn><eissn>1869-1889</eissn><abstract>Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin (PG) formation by targeting cyclooxygenase (COX) 1 and 2. Long-term use of NSAIDs that selectively inhibit COX2 increases the risk for thrombotic events, cardiac failure, and hypertension. However, the underlying mechanisms remain unclear. In this study, COX1- and COX2-deficient rats were created via Cas9/RNA-mediated gene targeting. DNA genotyping and Western blot analysis confirmed successful generation of COX1 −/− and COX2 −/− rats. Adult COX1 −/− rats grew normally, while more than 70% of COX2 −/− rats after wean died within 2 months. Echocardiography showed markedly reduced left ventricular ejection fraction and fractional shortening in adult COX2 −/− rats compared to those in wildtype (WT) controls. Histological analysis revealed accumulation of inflammatory cells and severe interstitial and perivascular fibrosis in COX2 −/− cardiac tissues. Moreover, cardiac ATP and acetyl-CoA production was dramatically decreased in COX2 −/− rats. Consistently, the expression of genes related to mitochondrial oxidation, such as those that encode for subunits of pyruvate dehydrogenase complex and acyl CoA dehydrogenases, were downregulated, while glycolytic hexokinase 1 (HK1) was upregulated in COX2 −/− heart tissues. These observations indicate that COX2-deficient rats developed spontaneously heart failure, likely as a result of dysregulated cardiac energy metabolism.</abstract><cop>Beijing</cop><pub>Science China Press</pub><pmid>32955658</pmid><doi>10.1007/s11427-020-1792-5</doi><tpages>9</tpages></addata></record>
fulltext	fulltext
identifier	ISSN: 1674-7305
ispartof	Science China. Life sciences, 2021-07, Vol.64 (7), p.1068-1076
issn	1674-7305 1869-1889
language	eng
recordid	cdi_proquest_miscellaneous_2444608435
source	MEDLINE; SpringerNature Journals; Alma/SFX Local Collection
subjects	Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology Biomarkers - metabolism Biomedical and Life Sciences Congestive heart failure Cyclooxygenase 1 - metabolism Cyclooxygenase 2 - metabolism Cyclooxygenase 2 Inhibitors - pharmacology Cyclooxygenase-1 Cyclooxygenase-2 Echocardiography Energy Metabolism Fibrosis Gene targeting Genotype Genotyping Glycolysis Heart failure Heart Failure - diagnostic imaging Heart Failure - drug therapy Heart Failure - metabolism Hexokinase Inflammation Life Sciences Mitochondria Nonsteroidal anti-inflammatory drugs Oxidation Pyruvate dehydrogenase (lipoamide) Pyruvic acid Rats Rats, Sprague-Dawley Research Paper Stroke Volume Ventricle
title	Congestive heart failure in COX2 deficient rats
url	https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T05%3A48%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Congestive%20heart%20failure%20in%20COX2%20deficient%20rats&rft.jtitle=Science%20China.%20Life%20sciences&rft.au=Wan,%20Qiangyou&rft.date=2021-07-01&rft.volume=64&rft.issue=7&rft.spage=1068&rft.epage=1076&rft.pages=1068-1076&rft.issn=1674-7305&rft.eissn=1869-1889&rft_id=info:doi/10.1007/s11427-020-1792-5&rft_dat=%3Cproquest_cross%3E2547980282%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2547980282&rft_id=info:pmid/32955658&rfr_iscdi=true