Preoperative gene expression may be associated with neurocognitive decline after cardiopulmonary bypass
Objective Despite advances in surgical techniques, neurocognitive decline after cardiopulmonary bypass remains a common and serious complication. We have previously demonstrated that patients with neurocognitive decline have unique genetic responses 6 hours after cardiopulmonary bypass when compared...
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| Veröffentlicht in: | The Journal of thoracic and cardiovascular surgery 2015-02, Vol.149 (2), p.613-623 |
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| container_title | The Journal of thoracic and cardiovascular surgery |
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| creator | Sabe, Ashraf A., MD Dalal, Rahul S., BS Chu, Louis M., MD Elmadhun, Nassrene Y., MD Ramlawi, Basel, MD Bianchi, Cesario, MD, PhD Sellke, Frank W., MD |
| description | Objective Despite advances in surgical techniques, neurocognitive decline after cardiopulmonary bypass remains a common and serious complication. We have previously demonstrated that patients with neurocognitive decline have unique genetic responses 6 hours after cardiopulmonary bypass when compared with normal patients. We used genomic microarray to objectively investigate whether patients with neurocognitive decline had associated preoperative gene expression profiles and how these profiles changed up to 4 days after surgery. Methods Patients undergoing cardiac surgery underwent neurocognitive assessments preoperatively and 4 days after surgery. Skeletal muscle was collected intraoperatively. Whole blood collected before cardiopulmonary bypass, 6 hours after cardiopulmonary bypass, and on postoperative day 4 was hybridized to Affymetrix Gene Chip U133 Plus 2.0 microarrays (Affymetrix Inc, Santa Clara, Calif). Gene expression in patients with neurocognitive decline was compared with gene expression in the normal group using JMP Genomics (SAS Institute Inc, Cary, NC). Only genes that were commonly expressed in the 2 groups with a false discovery rate of 0.05 and a fold change greater than 1.5 were carried forward to pathway analysis using Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, Calif). Microarray gene expression was validated by Green real-time polymerase chain reaction and Western blotting. Results Neurocognitive decline developed in 17 of 42 patients. A total of 54,675 common transcripts were identified on microarray in each group across all time points. Preoperatively, there were 140 genes that were significantly altered between the normal and neurocognitive decline groups ( P |
| doi_str_mv | 10.1016/j.jtcvs.2014.10.050 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4207964</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0022522314015554</els_id><sourcerecordid>1660437464</sourcerecordid><originalsourceid>FETCH-LOGICAL-c514t-dfbe8d00518aff2233e7eea08ef653def71bf8515ab64b6fb0cdfccf8ee9af9b3</originalsourceid><addsrcrecordid>eNqFkl2L1DAUhoMo7rj6CwTppTcdT9qkHxcuyKKrsKCggnchTU5mU9ukJu3o_PtNZ9ZFvfEqcPI-J4c8h5DnFLYUaPWq3_az2sdtAZSlyhY4PCAbCm2dVw3_9pBsAIoi50VRnpEnMfYAUANtH5OzgrOmbKHYkN2ngH7CIGe7x2yHDjP8NQWM0XqXjfKQdZjJGL2yckad_bTzTeZwCV75nbNHSqMabAKlmTFkSgZt_bQMo3cyJP4wJf4peWTkEPHZ3XlOvr57--XyfX798erD5ZvrXHHK5lybDhsNwGkjjUmTl1gjSmjQVLzUaGramYZTLruKdZXpQGmjlGkQW2narjwnF6e-09KNqBW6OchBTMGOaRjhpRV_3zh7I3Z-L1gBdVux1ODlXYPgfywYZzHaqHAYpEO_REGrClhZs2O0PEVV8DEGNPfPUBCrItGLoyKxKlqLSVGiXvw54T3z20kKvD4FMP3T3mIQUVl0CrUNqGahvf3PAxf_8Kseq-TwHQ8Ye78ElxQIKmIhQHxet2RdEsqAcs5ZeQsY-75J</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1660437464</pqid></control><display><type>article</type><title>Preoperative gene expression may be associated with neurocognitive decline after cardiopulmonary bypass</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Sabe, Ashraf A., MD ; Dalal, Rahul S., BS ; Chu, Louis M., MD ; Elmadhun, Nassrene Y., MD ; Ramlawi, Basel, MD ; Bianchi, Cesario, MD, PhD ; Sellke, Frank W., MD</creator><creatorcontrib>Sabe, Ashraf A., MD ; Dalal, Rahul S., BS ; Chu, Louis M., MD ; Elmadhun, Nassrene Y., MD ; Ramlawi, Basel, MD ; Bianchi, Cesario, MD, PhD ; Sellke, Frank W., MD</creatorcontrib><description>Objective Despite advances in surgical techniques, neurocognitive decline after cardiopulmonary bypass remains a common and serious complication. We have previously demonstrated that patients with neurocognitive decline have unique genetic responses 6 hours after cardiopulmonary bypass when compared with normal patients. We used genomic microarray to objectively investigate whether patients with neurocognitive decline had associated preoperative gene expression profiles and how these profiles changed up to 4 days after surgery. Methods Patients undergoing cardiac surgery underwent neurocognitive assessments preoperatively and 4 days after surgery. Skeletal muscle was collected intraoperatively. Whole blood collected before cardiopulmonary bypass, 6 hours after cardiopulmonary bypass, and on postoperative day 4 was hybridized to Affymetrix Gene Chip U133 Plus 2.0 microarrays (Affymetrix Inc, Santa Clara, Calif). Gene expression in patients with neurocognitive decline was compared with gene expression in the normal group using JMP Genomics (SAS Institute Inc, Cary, NC). Only genes that were commonly expressed in the 2 groups with a false discovery rate of 0.05 and a fold change greater than 1.5 were carried forward to pathway analysis using Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, Calif). Microarray gene expression was validated by Green real-time polymerase chain reaction and Western blotting. Results Neurocognitive decline developed in 17 of 42 patients. A total of 54,675 common transcripts were identified on microarray in each group across all time points. Preoperatively, there were 140 genes that were significantly altered between the normal and neurocognitive decline groups ( P < .05). Pathway analysis demonstrated that preoperatively, patients with neurocognitive decline had increased regulation in genes associated with inflammation, cell death, and neurologic dysfunction. Of note, the number of significantly regulated genes between the 2 groups changed over each time point and decreased from 140 preoperatively to 64 six hours after cardiopulmonary bypass and to 25 four days after surgery. There was no correlation in gene expression between the blood and the skeletal muscle. Conclusions Patients in whom neurocognitive decline developed after cardiopulmonary bypass had increased differential gene expression before surgery versus patients in whom neurocognitive decline did not develop. Although significant differences in gene expression also existed postoperatively, these differences gradually decreased over time. Preoperative gene expression may be associated with neurologic injury after cardiopulmonary bypass. Further investigation into these genetic pathways may help predict patient outcome and guide patient selection.</description><identifier>ISSN: 0022-5223</identifier><identifier>EISSN: 1097-685X</identifier><identifier>DOI: 10.1016/j.jtcvs.2014.10.050</identifier><identifier>PMID: 25483902</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Blotting, Western ; Cardiopulmonary Bypass ; Cardiothoracic Surgery ; Cognition Disorders - genetics ; Disease Progression ; Female ; Gene Expression Profiling ; Humans ; Male ; Real-Time Polymerase Chain Reaction</subject><ispartof>The Journal of thoracic and cardiovascular surgery, 2015-02, Vol.149 (2), p.613-623</ispartof><rights>The American Association for Thoracic Surgery</rights><rights>2015 The American Association for Thoracic Surgery</rights><rights>Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-dfbe8d00518aff2233e7eea08ef653def71bf8515ab64b6fb0cdfccf8ee9af9b3</citedby><cites>FETCH-LOGICAL-c514t-dfbe8d00518aff2233e7eea08ef653def71bf8515ab64b6fb0cdfccf8ee9af9b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022522314015554$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25483902$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sabe, Ashraf A., MD</creatorcontrib><creatorcontrib>Dalal, Rahul S., BS</creatorcontrib><creatorcontrib>Chu, Louis M., MD</creatorcontrib><creatorcontrib>Elmadhun, Nassrene Y., MD</creatorcontrib><creatorcontrib>Ramlawi, Basel, MD</creatorcontrib><creatorcontrib>Bianchi, Cesario, MD, PhD</creatorcontrib><creatorcontrib>Sellke, Frank W., MD</creatorcontrib><title>Preoperative gene expression may be associated with neurocognitive decline after cardiopulmonary bypass</title><title>The Journal of thoracic and cardiovascular surgery</title><addtitle>J Thorac Cardiovasc Surg</addtitle><description>Objective Despite advances in surgical techniques, neurocognitive decline after cardiopulmonary bypass remains a common and serious complication. We have previously demonstrated that patients with neurocognitive decline have unique genetic responses 6 hours after cardiopulmonary bypass when compared with normal patients. We used genomic microarray to objectively investigate whether patients with neurocognitive decline had associated preoperative gene expression profiles and how these profiles changed up to 4 days after surgery. Methods Patients undergoing cardiac surgery underwent neurocognitive assessments preoperatively and 4 days after surgery. Skeletal muscle was collected intraoperatively. Whole blood collected before cardiopulmonary bypass, 6 hours after cardiopulmonary bypass, and on postoperative day 4 was hybridized to Affymetrix Gene Chip U133 Plus 2.0 microarrays (Affymetrix Inc, Santa Clara, Calif). Gene expression in patients with neurocognitive decline was compared with gene expression in the normal group using JMP Genomics (SAS Institute Inc, Cary, NC). Only genes that were commonly expressed in the 2 groups with a false discovery rate of 0.05 and a fold change greater than 1.5 were carried forward to pathway analysis using Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, Calif). Microarray gene expression was validated by Green real-time polymerase chain reaction and Western blotting. Results Neurocognitive decline developed in 17 of 42 patients. A total of 54,675 common transcripts were identified on microarray in each group across all time points. Preoperatively, there were 140 genes that were significantly altered between the normal and neurocognitive decline groups ( P < .05). Pathway analysis demonstrated that preoperatively, patients with neurocognitive decline had increased regulation in genes associated with inflammation, cell death, and neurologic dysfunction. Of note, the number of significantly regulated genes between the 2 groups changed over each time point and decreased from 140 preoperatively to 64 six hours after cardiopulmonary bypass and to 25 four days after surgery. There was no correlation in gene expression between the blood and the skeletal muscle. Conclusions Patients in whom neurocognitive decline developed after cardiopulmonary bypass had increased differential gene expression before surgery versus patients in whom neurocognitive decline did not develop. Although significant differences in gene expression also existed postoperatively, these differences gradually decreased over time. Preoperative gene expression may be associated with neurologic injury after cardiopulmonary bypass. Further investigation into these genetic pathways may help predict patient outcome and guide patient selection.</description><subject>Blotting, Western</subject><subject>Cardiopulmonary Bypass</subject><subject>Cardiothoracic Surgery</subject><subject>Cognition Disorders - genetics</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Male</subject><subject>Real-Time Polymerase Chain Reaction</subject><issn>0022-5223</issn><issn>1097-685X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkl2L1DAUhoMo7rj6CwTppTcdT9qkHxcuyKKrsKCggnchTU5mU9ukJu3o_PtNZ9ZFvfEqcPI-J4c8h5DnFLYUaPWq3_az2sdtAZSlyhY4PCAbCm2dVw3_9pBsAIoi50VRnpEnMfYAUANtH5OzgrOmbKHYkN2ngH7CIGe7x2yHDjP8NQWM0XqXjfKQdZjJGL2yckad_bTzTeZwCV75nbNHSqMabAKlmTFkSgZt_bQMo3cyJP4wJf4peWTkEPHZ3XlOvr57--XyfX798erD5ZvrXHHK5lybDhsNwGkjjUmTl1gjSmjQVLzUaGramYZTLruKdZXpQGmjlGkQW2narjwnF6e-09KNqBW6OchBTMGOaRjhpRV_3zh7I3Z-L1gBdVux1ODlXYPgfywYZzHaqHAYpEO_REGrClhZs2O0PEVV8DEGNPfPUBCrItGLoyKxKlqLSVGiXvw54T3z20kKvD4FMP3T3mIQUVl0CrUNqGahvf3PAxf_8Kseq-TwHQ8Ye78ElxQIKmIhQHxet2RdEsqAcs5ZeQsY-75J</recordid><startdate>20150201</startdate><enddate>20150201</enddate><creator>Sabe, Ashraf A., MD</creator><creator>Dalal, Rahul S., BS</creator><creator>Chu, Louis M., MD</creator><creator>Elmadhun, Nassrene Y., MD</creator><creator>Ramlawi, Basel, MD</creator><creator>Bianchi, Cesario, MD, PhD</creator><creator>Sellke, Frank W., MD</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150201</creationdate><title>Preoperative gene expression may be associated with neurocognitive decline after cardiopulmonary bypass</title><author>Sabe, Ashraf A., MD ; Dalal, Rahul S., BS ; Chu, Louis M., MD ; Elmadhun, Nassrene Y., MD ; Ramlawi, Basel, MD ; Bianchi, Cesario, MD, PhD ; Sellke, Frank W., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-dfbe8d00518aff2233e7eea08ef653def71bf8515ab64b6fb0cdfccf8ee9af9b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Blotting, Western</topic><topic>Cardiopulmonary Bypass</topic><topic>Cardiothoracic Surgery</topic><topic>Cognition Disorders - genetics</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Male</topic><topic>Real-Time Polymerase Chain Reaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sabe, Ashraf A., MD</creatorcontrib><creatorcontrib>Dalal, Rahul S., BS</creatorcontrib><creatorcontrib>Chu, Louis M., MD</creatorcontrib><creatorcontrib>Elmadhun, Nassrene Y., MD</creatorcontrib><creatorcontrib>Ramlawi, Basel, MD</creatorcontrib><creatorcontrib>Bianchi, Cesario, MD, PhD</creatorcontrib><creatorcontrib>Sellke, Frank W., MD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sabe, Ashraf A., MD</au><au>Dalal, Rahul S., BS</au><au>Chu, Louis M., MD</au><au>Elmadhun, Nassrene Y., MD</au><au>Ramlawi, Basel, MD</au><au>Bianchi, Cesario, MD, PhD</au><au>Sellke, Frank W., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preoperative gene expression may be associated with neurocognitive decline after cardiopulmonary bypass</atitle><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle><addtitle>J Thorac Cardiovasc Surg</addtitle><date>2015-02-01</date><risdate>2015</risdate><volume>149</volume><issue>2</issue><spage>613</spage><epage>623</epage><pages>613-623</pages><issn>0022-5223</issn><eissn>1097-685X</eissn><abstract>Objective Despite advances in surgical techniques, neurocognitive decline after cardiopulmonary bypass remains a common and serious complication. We have previously demonstrated that patients with neurocognitive decline have unique genetic responses 6 hours after cardiopulmonary bypass when compared with normal patients. We used genomic microarray to objectively investigate whether patients with neurocognitive decline had associated preoperative gene expression profiles and how these profiles changed up to 4 days after surgery. Methods Patients undergoing cardiac surgery underwent neurocognitive assessments preoperatively and 4 days after surgery. Skeletal muscle was collected intraoperatively. Whole blood collected before cardiopulmonary bypass, 6 hours after cardiopulmonary bypass, and on postoperative day 4 was hybridized to Affymetrix Gene Chip U133 Plus 2.0 microarrays (Affymetrix Inc, Santa Clara, Calif). Gene expression in patients with neurocognitive decline was compared with gene expression in the normal group using JMP Genomics (SAS Institute Inc, Cary, NC). Only genes that were commonly expressed in the 2 groups with a false discovery rate of 0.05 and a fold change greater than 1.5 were carried forward to pathway analysis using Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, Calif). Microarray gene expression was validated by Green real-time polymerase chain reaction and Western blotting. Results Neurocognitive decline developed in 17 of 42 patients. A total of 54,675 common transcripts were identified on microarray in each group across all time points. Preoperatively, there were 140 genes that were significantly altered between the normal and neurocognitive decline groups ( P < .05). Pathway analysis demonstrated that preoperatively, patients with neurocognitive decline had increased regulation in genes associated with inflammation, cell death, and neurologic dysfunction. Of note, the number of significantly regulated genes between the 2 groups changed over each time point and decreased from 140 preoperatively to 64 six hours after cardiopulmonary bypass and to 25 four days after surgery. There was no correlation in gene expression between the blood and the skeletal muscle. Conclusions Patients in whom neurocognitive decline developed after cardiopulmonary bypass had increased differential gene expression before surgery versus patients in whom neurocognitive decline did not develop. Although significant differences in gene expression also existed postoperatively, these differences gradually decreased over time. Preoperative gene expression may be associated with neurologic injury after cardiopulmonary bypass. Further investigation into these genetic pathways may help predict patient outcome and guide patient selection.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25483902</pmid><doi>10.1016/j.jtcvs.2014.10.050</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Blotting, Western Cardiopulmonary Bypass Cardiothoracic Surgery Cognition Disorders - genetics Disease Progression Female Gene Expression Profiling Humans Male Real-Time Polymerase Chain Reaction |
| title | Preoperative gene expression may be associated with neurocognitive decline after cardiopulmonary bypass |
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