Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest
Deep hypothermic circulatory arrest (DHCA) has been used in cardiac surgery involving infant complex congenital heart disease and aortic dissection. DHCA carries a risk of neuronal apoptotic death in brain. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) level is elevated in a number of neurologica...
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Veröffentlicht in: | International journal of medical sciences 2015-01, Vol.12 (7), p.576-582 |
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description | Deep hypothermic circulatory arrest (DHCA) has been used in cardiac surgery involving infant complex congenital heart disease and aortic dissection. DHCA carries a risk of neuronal apoptotic death in brain. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) level is elevated in a number of neurological diseases involving neuron injury and death. We studied the hypothesis that UCH-L1 may be a potential biomarker for DHCA-induced ischemic neuronal apoptosis.
Anesthetized piglets were used to perform cardiopulmonary bypass (CPB). DHCA was induced for 1 hour followed by CPB rewarming. Blood samples were collected and serum UCH-L1 levels were measured. Neuron apoptosis and Bax and Bcl-2 proteins in hippocampus were examined. The relationship between neuron apoptosis and UCH-L1 level was determined by receiver operating characteristics (ROC) curves and correlation analysis.
DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P |
doi_str_mv | 10.7150/ijms.12111 |
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Anesthetized piglets were used to perform cardiopulmonary bypass (CPB). DHCA was induced for 1 hour followed by CPB rewarming. Blood samples were collected and serum UCH-L1 levels were measured. Neuron apoptosis and Bax and Bcl-2 proteins in hippocampus were examined. The relationship between neuron apoptosis and UCH-L1 level was determined by receiver operating characteristics (ROC) curves and correlation analysis.
DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P<0.05). Positive correlation was obtained between serum UCH-L1 level and the severity of neuron apoptosis (r= 0.78, P<0.01). By ROC, the area under the curve were 0.88 (95% CI: 0.74-0.99; P<0.01), 0.81 (95% CI: 0.81-0.96; P<0.05), 0.71 (95% CI: 0.47-0.92; P=0.11) for UCH-L1, Bax/Bcl-2 ratio and Bax, respectively. Using a cut-off point of 0.25, the UCH-L1 predicted neuronal apoptosis with a sensitivity of 85% and specificity of 57%.
Serum UCH-L1, as an easy and quick measurable biomarker, can predict neural apoptosis induced by DHCA. The elevation in UCH-L1 concentration is consistent with the severity of neural apoptosis following DHCA.</description><identifier>ISSN: 1449-1907</identifier><identifier>EISSN: 1449-1907</identifier><identifier>DOI: 10.7150/ijms.12111</identifier><identifier>PMID: 26180514</identifier><language>eng</language><publisher>Australia: Ivyspring International Publisher</publisher><subject>Animals ; Apoptosis - genetics ; Biomarkers - blood ; Brain Ischemia - blood ; Brain Ischemia - etiology ; Brain Ischemia - physiopathology ; Cardiac Surgical Procedures - adverse effects ; Cardiopulmonary Bypass - adverse effects ; Circulatory Arrest, Deep Hypothermia Induced ; Hippocampus - pathology ; Humans ; Neurons - pathology ; Research Paper ; Swine ; Ubiquitin Thiolesterase - blood ; Ubiquitin Thiolesterase - genetics</subject><ispartof>International journal of medical sciences, 2015-01, Vol.12 (7), p.576-582</ispartof><rights>2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. 2015</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-bf6746af4f508d67b6e204630cc4be4cb9dfc13ecdb7051ad0046779fee5b4db3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502062/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502062/$$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/26180514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Ya-Ping</creatorcontrib><creatorcontrib>Zhu, Yao-Bin</creatorcontrib><creatorcontrib>Duan, Dayue Darrel</creatorcontrib><creatorcontrib>Fan, Xiang-Ming</creatorcontrib><creatorcontrib>He, Yan</creatorcontrib><creatorcontrib>Su, Jun-Wu</creatorcontrib><creatorcontrib>Liu, Ying-Long</creatorcontrib><title>Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest</title><title>International journal of medical sciences</title><addtitle>Int J Med Sci</addtitle><description>Deep hypothermic circulatory arrest (DHCA) has been used in cardiac surgery involving infant complex congenital heart disease and aortic dissection. DHCA carries a risk of neuronal apoptotic death in brain. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) level is elevated in a number of neurological diseases involving neuron injury and death. We studied the hypothesis that UCH-L1 may be a potential biomarker for DHCA-induced ischemic neuronal apoptosis.
Anesthetized piglets were used to perform cardiopulmonary bypass (CPB). DHCA was induced for 1 hour followed by CPB rewarming. Blood samples were collected and serum UCH-L1 levels were measured. Neuron apoptosis and Bax and Bcl-2 proteins in hippocampus were examined. The relationship between neuron apoptosis and UCH-L1 level was determined by receiver operating characteristics (ROC) curves and correlation analysis.
DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P<0.05). Positive correlation was obtained between serum UCH-L1 level and the severity of neuron apoptosis (r= 0.78, P<0.01). By ROC, the area under the curve were 0.88 (95% CI: 0.74-0.99; P<0.01), 0.81 (95% CI: 0.81-0.96; P<0.05), 0.71 (95% CI: 0.47-0.92; P=0.11) for UCH-L1, Bax/Bcl-2 ratio and Bax, respectively. Using a cut-off point of 0.25, the UCH-L1 predicted neuronal apoptosis with a sensitivity of 85% and specificity of 57%.
Serum UCH-L1, as an easy and quick measurable biomarker, can predict neural apoptosis induced by DHCA. The elevation in UCH-L1 concentration is consistent with the severity of neural apoptosis following DHCA.</description><subject>Animals</subject><subject>Apoptosis - genetics</subject><subject>Biomarkers - blood</subject><subject>Brain Ischemia - blood</subject><subject>Brain Ischemia - etiology</subject><subject>Brain Ischemia - physiopathology</subject><subject>Cardiac Surgical Procedures - adverse effects</subject><subject>Cardiopulmonary Bypass - adverse effects</subject><subject>Circulatory Arrest, Deep Hypothermia Induced</subject><subject>Hippocampus - pathology</subject><subject>Humans</subject><subject>Neurons - pathology</subject><subject>Research Paper</subject><subject>Swine</subject><subject>Ubiquitin Thiolesterase - blood</subject><subject>Ubiquitin Thiolesterase - genetics</subject><issn>1449-1907</issn><issn>1449-1907</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUVtLwzAYDaK4eXnxB0geRagmbZqsL8KczglDBfU5pOlXl5k2NWkn-_d23tCn74NzOBcOQkeUnAmaknOzrMIZjSmlW2hIGcsimhGx_ecfoL0QloQkcSLoLhrEnI5IStkQVY_guwo_T2bRnGIVsMJ3bgUWXxpXKf8KHrcOP3gojG7xHXTe1criceOa1gUT8NRZ695N_YKvABo8WzeuXYCvjMYT43VnVev8Go-9h9AeoJ1S2QCH33cfPU-vnzbe9ze3k_E80okYtVFecsG4KlmZklHBRc4hJownRGuWA9N5VpSaJqCLXPQ1VEF6VIisBEhzVuTJPrr40m26vIJCQ916ZWXjTd9pLZ0y8j9Sm4V8cSvJUhITHvcCJ98C3r11fXJZmaDBWlWD64KkPBMx5XFKeurpF1V7F4KH8teGErnZR272kZ_79OTjv8F-qT-DJB_iPo4y</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Zhang, Ya-Ping</creator><creator>Zhu, Yao-Bin</creator><creator>Duan, Dayue Darrel</creator><creator>Fan, Xiang-Ming</creator><creator>He, Yan</creator><creator>Su, Jun-Wu</creator><creator>Liu, Ying-Long</creator><general>Ivyspring International Publisher</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150101</creationdate><title>Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest</title><author>Zhang, Ya-Ping ; Zhu, Yao-Bin ; Duan, Dayue Darrel ; Fan, Xiang-Ming ; He, Yan ; Su, Jun-Wu ; Liu, Ying-Long</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-bf6746af4f508d67b6e204630cc4be4cb9dfc13ecdb7051ad0046779fee5b4db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Apoptosis - genetics</topic><topic>Biomarkers - blood</topic><topic>Brain Ischemia - blood</topic><topic>Brain Ischemia - etiology</topic><topic>Brain Ischemia - physiopathology</topic><topic>Cardiac Surgical Procedures - adverse effects</topic><topic>Cardiopulmonary Bypass - adverse effects</topic><topic>Circulatory Arrest, Deep Hypothermia Induced</topic><topic>Hippocampus - pathology</topic><topic>Humans</topic><topic>Neurons - pathology</topic><topic>Research Paper</topic><topic>Swine</topic><topic>Ubiquitin Thiolesterase - blood</topic><topic>Ubiquitin Thiolesterase - genetics</topic><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Ya-Ping</creatorcontrib><creatorcontrib>Zhu, Yao-Bin</creatorcontrib><creatorcontrib>Duan, Dayue Darrel</creatorcontrib><creatorcontrib>Fan, Xiang-Ming</creatorcontrib><creatorcontrib>He, Yan</creatorcontrib><creatorcontrib>Su, Jun-Wu</creatorcontrib><creatorcontrib>Liu, Ying-Long</creatorcontrib><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>International journal of medical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Ya-Ping</au><au>Zhu, Yao-Bin</au><au>Duan, Dayue Darrel</au><au>Fan, Xiang-Ming</au><au>He, Yan</au><au>Su, Jun-Wu</au><au>Liu, Ying-Long</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest</atitle><jtitle>International journal of medical sciences</jtitle><addtitle>Int J Med Sci</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>12</volume><issue>7</issue><spage>576</spage><epage>582</epage><pages>576-582</pages><issn>1449-1907</issn><eissn>1449-1907</eissn><abstract>Deep hypothermic circulatory arrest (DHCA) has been used in cardiac surgery involving infant complex congenital heart disease and aortic dissection. DHCA carries a risk of neuronal apoptotic death in brain. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) level is elevated in a number of neurological diseases involving neuron injury and death. We studied the hypothesis that UCH-L1 may be a potential biomarker for DHCA-induced ischemic neuronal apoptosis.
Anesthetized piglets were used to perform cardiopulmonary bypass (CPB). DHCA was induced for 1 hour followed by CPB rewarming. Blood samples were collected and serum UCH-L1 levels were measured. Neuron apoptosis and Bax and Bcl-2 proteins in hippocampus were examined. The relationship between neuron apoptosis and UCH-L1 level was determined by receiver operating characteristics (ROC) curves and correlation analysis.
DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P<0.05). Positive correlation was obtained between serum UCH-L1 level and the severity of neuron apoptosis (r= 0.78, P<0.01). By ROC, the area under the curve were 0.88 (95% CI: 0.74-0.99; P<0.01), 0.81 (95% CI: 0.81-0.96; P<0.05), 0.71 (95% CI: 0.47-0.92; P=0.11) for UCH-L1, Bax/Bcl-2 ratio and Bax, respectively. Using a cut-off point of 0.25, the UCH-L1 predicted neuronal apoptosis with a sensitivity of 85% and specificity of 57%.
Serum UCH-L1, as an easy and quick measurable biomarker, can predict neural apoptosis induced by DHCA. The elevation in UCH-L1 concentration is consistent with the severity of neural apoptosis following DHCA.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher</pub><pmid>26180514</pmid><doi>10.7150/ijms.12111</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Apoptosis - genetics Biomarkers - blood Brain Ischemia - blood Brain Ischemia - etiology Brain Ischemia - physiopathology Cardiac Surgical Procedures - adverse effects Cardiopulmonary Bypass - adverse effects Circulatory Arrest, Deep Hypothermia Induced Hippocampus - pathology Humans Neurons - pathology Research Paper Swine Ubiquitin Thiolesterase - blood Ubiquitin Thiolesterase - genetics |
title | Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest |
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