Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane
Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have imp...
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| creator | Park, Sung-Hyun Lu, Yuting Shao, Yongzhao Prophete, Colette Horton, Lori Sisco, Maureen Lee, Hyun-Wook Kluz, Thomas Sun, Hong Costa, Max Zelikoff, Judith Chen, Lung-Chi Cohen, Mitchell D |
| description | Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated. |
| doi_str_mv | 10.1371/journal.pone.0257241 |
| format | Article |
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Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0257241</identifier><identifier>PMID: 34648499</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Abnormalities ; Adhesion ; Analysis ; Angiogenesis ; Animal models ; Biology and Life Sciences ; Blood pressure ; Cell differentiation ; Cell migration ; Cell signaling ; Circadian rhythms ; Complications and side effects ; Congestive heart failure ; Earth Sciences ; Elongation ; Environmental health ; Exposure ; Extracellular matrix ; Gene expression ; Gene regulation ; Genes ; Genetic transcription ; Heart failure ; Hypertension ; Immune response ; Inhalation ; Isoflurane ; Laboratory animals ; Medicine ; Medicine and Health Sciences ; Mitochondria ; Oxidative phosphorylation ; Patient outcomes ; Phosphorylation ; Physical Sciences ; Research and Analysis Methods ; Respiration ; Side effects ; Substrates ; Tissues ; Trachea ; Translation elongation ; Ventricle ; Wounding</subject><ispartof>PloS one, 2021-10, Vol.16 (10), p.e0257241</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Park et al 2021 Park et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c669t-d984219d9579d7755dd1f6aea95691aceb43c8e9507d0dd3b03e858fa7aafa143</citedby><cites>FETCH-LOGICAL-c669t-d984219d9579d7755dd1f6aea95691aceb43c8e9507d0dd3b03e858fa7aafa143</cites><orcidid>0000-0002-9378-0012</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/PMC8516213/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516213/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids></links><search><contributor>Joles, Jaap A.</contributor><creatorcontrib>Park, Sung-Hyun</creatorcontrib><creatorcontrib>Lu, Yuting</creatorcontrib><creatorcontrib>Shao, Yongzhao</creatorcontrib><creatorcontrib>Prophete, Colette</creatorcontrib><creatorcontrib>Horton, Lori</creatorcontrib><creatorcontrib>Sisco, Maureen</creatorcontrib><creatorcontrib>Lee, Hyun-Wook</creatorcontrib><creatorcontrib>Kluz, Thomas</creatorcontrib><creatorcontrib>Sun, Hong</creatorcontrib><creatorcontrib>Costa, Max</creatorcontrib><creatorcontrib>Zelikoff, Judith</creatorcontrib><creatorcontrib>Chen, Lung-Chi</creatorcontrib><creatorcontrib>Cohen, Mitchell D</creatorcontrib><title>Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane</title><title>PloS one</title><description>Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.</description><subject>Abnormalities</subject><subject>Adhesion</subject><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Biology and Life Sciences</subject><subject>Blood pressure</subject><subject>Cell differentiation</subject><subject>Cell migration</subject><subject>Cell signaling</subject><subject>Circadian rhythms</subject><subject>Complications and side effects</subject><subject>Congestive heart failure</subject><subject>Earth Sciences</subject><subject>Elongation</subject><subject>Environmental health</subject><subject>Exposure</subject><subject>Extracellular matrix</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genetic transcription</subject><subject>Heart failure</subject><subject>Hypertension</subject><subject>Immune response</subject><subject>Inhalation</subject><subject>Isoflurane</subject><subject>Laboratory animals</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mitochondria</subject><subject>Oxidative phosphorylation</subject><subject>Patient outcomes</subject><subject>Phosphorylation</subject><subject>Physical Sciences</subject><subject>Research and Analysis Methods</subject><subject>Respiration</subject><subject>Side effects</subject><subject>Substrates</subject><subject>Tissues</subject><subject>Trachea</subject><subject>Translation 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impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane</title><author>Park, Sung-Hyun ; Lu, Yuting ; Shao, Yongzhao ; Prophete, Colette ; Horton, Lori ; Sisco, Maureen ; Lee, Hyun-Wook ; Kluz, Thomas ; Sun, Hong ; Costa, Max ; Zelikoff, Judith ; Chen, Lung-Chi ; Cohen, Mitchell D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c669t-d984219d9579d7755dd1f6aea95691aceb43c8e9507d0dd3b03e858fa7aafa143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Abnormalities</topic><topic>Adhesion</topic><topic>Analysis</topic><topic>Angiogenesis</topic><topic>Animal models</topic><topic>Biology and Life Sciences</topic><topic>Blood pressure</topic><topic>Cell differentiation</topic><topic>Cell migration</topic><topic>Cell signaling</topic><topic>Circadian rhythms</topic><topic>Complications and side 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(Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Sung-Hyun</au><au>Lu, Yuting</au><au>Shao, Yongzhao</au><au>Prophete, Colette</au><au>Horton, Lori</au><au>Sisco, Maureen</au><au>Lee, Hyun-Wook</au><au>Kluz, Thomas</au><au>Sun, Hong</au><au>Costa, Max</au><au>Zelikoff, Judith</au><au>Chen, Lung-Chi</au><au>Cohen, Mitchell D</au><au>Joles, Jaap A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane</atitle><jtitle>PloS one</jtitle><date>2021-10-14</date><risdate>2021</risdate><volume>16</volume><issue>10</issue><spage>e0257241</spage><pages>e0257241-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34648499</pmid><doi>10.1371/journal.pone.0257241</doi><tpages>e0257241</tpages><orcidid>https://orcid.org/0000-0002-9378-0012</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2021-10, Vol.16 (10), p.e0257241 |
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| source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Abnormalities Adhesion Analysis Angiogenesis Animal models Biology and Life Sciences Blood pressure Cell differentiation Cell migration Cell signaling Circadian rhythms Complications and side effects Congestive heart failure Earth Sciences Elongation Environmental health Exposure Extracellular matrix Gene expression Gene regulation Genes Genetic transcription Heart failure Hypertension Immune response Inhalation Isoflurane Laboratory animals Medicine Medicine and Health Sciences Mitochondria Oxidative phosphorylation Patient outcomes Phosphorylation Physical Sciences Research and Analysis Methods Respiration Side effects Substrates Tissues Trachea Translation elongation Ventricle Wounding |
| title | Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T12%3A21%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Longitudinal%20impact%20on%20rat%20cardiac%20tissue%20transcriptomic%20profiles%20due%20to%20acute%20intratracheal%20inhalation%20exposures%20to%20isoflurane&rft.jtitle=PloS%20one&rft.au=Park,%20Sung-Hyun&rft.date=2021-10-14&rft.volume=16&rft.issue=10&rft.spage=e0257241&rft.pages=e0257241-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0257241&rft_dat=%3Cgale_plos_%3EA678973870%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2582105326&rft_id=info:pmid/34648499&rft_galeid=A678973870&rft_doaj_id=oai_doaj_org_article_448ef4967a854807963659a33b140da9&rfr_iscdi=true |