Reciprocal Changes of Circulating Long Non-Coding RNAs ZFAS1 and CDR1AS Predict Acute Myocardial Infarction

This study sought to evaluate the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers for acute myocardial infarction (AMI). We measured the circulating levels of 15 individual lncRNAs, known to be relevant to cardiovascular disease, using the whole blood samples collected from 103...

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Published in:	Scientific reports Vol. 6; no. 1; p. 22384
Main Authors:	Zhang, Ying, Sun, Lihua, Xuan, Lina, Pan, Zhenwei, Li, Kang, Liu, Shuangshuang, Huang, Yuechao, Zhao, Xuyun, Huang, Lihua, Wang, Zhiguo, Hou, Yan, Li, Junnan, Tian, Ye, Yu, Jiahui, Han, Hui, Liu, Yanhong, Gao, Fei, Zhang, Yong, Wang, Shu, Du, Zhimin, Lu, Yanjie, Yang, Baofeng
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01.03.2016 Nature Publishing Group
Subjects:	38/90 692/4019/592/75/2/1674 692/53/2421 Animals Antisense RNA Biomarkers Biomarkers - blood Blood Cardiac arrhythmia Cardiovascular diseases Complementarity-determining region 1 Disease Models, Animal Heart attacks Humanities and Social Sciences Humans Mice Mice, Inbred C57BL Middle Aged multidisciplinary Myocardial infarction Myocardial Infarction - blood Myocardial Infarction - diagnosis Prognosis RNA, Long Noncoding - blood Rodents Science Zinc finger proteins
ISSN:	2045-2322, 2045-2322
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Abstract	This study sought to evaluate the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers for acute myocardial infarction (AMI). We measured the circulating levels of 15 individual lncRNAs, known to be relevant to cardiovascular disease, using the whole blood samples collected from 103 AMI patients, 149 non-AMI subjects and 95 healthy volunteers. We found that only two of them, Zinc finger antisense 1 ( ZFAS1 ) and Cdr1 antisense ( CDR1AS ), showed significant differential expression between AMI patients and control subjects. Circulating level of ZFAS1 was significantly lower in AMI (0.74 ± 0.07) than in non-AMI subjects (1.0 ± 0.05, P < 0.0001), whereas CDR1AS showed the opposite changes with its blood level markedly higher in AMI (2.18 ± 0.24) than in non-AMI subjects (1.0 ± 0.05, P < 0.0001). When comparison was made between AMI and non-AMI, the area under ROC curve was 0.664 for ZFAS1 alone or 0.671 for CDR1AS alone and 0.691 for ZFAS1 and CDR1AS combination. Univariate and multivariate analyses identified these two lncRNAs as independent predictors for AMI. Similar changes of circulating ZFAS1 and CDR1AS were consistently observed in an AMI mouse model. Reciprocal changes of circulating ZFAS1 and CDR1AS independently predict AMI and may be considered novel biomarkers of AMI.
AbstractList	This study sought to evaluate the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers for acute myocardial infarction (AMI). We measured the circulating levels of 15 individual lncRNAs, known to be relevant to cardiovascular disease, using the whole blood samples collected from 103 AMI patients, 149 non-AMI subjects, and 95 healthy volunteers. We found that only two of them, Zinc finger antisense 1 (ZFAS1) and Cdr1 antisense (CDR1AS), showed significant differential expression between AMI patients and control subjects. Circulating level of ZFAS1 was significantly lower in AMI (0.74 ± 0.07) than in non-AMI subjects (1.0 ± 0.05, P < 0.0001), whereas CDR1AS showed the opposite changes with its blood level markedly higher in AMI (2.18 ± 0.24) than in non-AMI subjects (1.0 ± 0.05, P < 0.0001). When comparison was made between AMI and non-AMI, the area under ROC curve was 0.664 for ZFAS1 alone or 0.671 for CDR1AS alone, and 0.691 for ZFAS1 and CDR1AS combination. Univariate and multivariate analyses identified these two lncRNAs as independent predictors for AMI. Similar changes of circulating ZFAS1 and CDR1AS were consistently observed in an AMI mouse model. Reciprocal changes of circulating ZFAS1 and CDR1AS independently predict AMI and may be considered novel biomarkers of AMI. This study sought to evaluate the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers for acute myocardial infarction (AMI). We measured the circulating levels of 15 individual lncRNAs, known to be relevant to cardiovascular disease, using the whole blood samples collected from 103 AMI patients, 149 non-AMI subjects and 95 healthy volunteers. We found that only two of them, Zinc finger antisense 1 ( ZFAS1 ) and Cdr1 antisense ( CDR1AS ), showed significant differential expression between AMI patients and control subjects. Circulating level of ZFAS1 was significantly lower in AMI (0.74 ± 0.07) than in non-AMI subjects (1.0 ± 0.05, P < 0.0001), whereas CDR1AS showed the opposite changes with its blood level markedly higher in AMI (2.18 ± 0.24) than in non-AMI subjects (1.0 ± 0.05, P < 0.0001). When comparison was made between AMI and non-AMI, the area under ROC curve was 0.664 for ZFAS1 alone or 0.671 for CDR1AS alone and 0.691 for ZFAS1 and CDR1AS combination. Univariate and multivariate analyses identified these two lncRNAs as independent predictors for AMI. Similar changes of circulating ZFAS1 and CDR1AS were consistently observed in an AMI mouse model. Reciprocal changes of circulating ZFAS1 and CDR1AS independently predict AMI and may be considered novel biomarkers of AMI.
ArticleNumber	22384
Author	Huang, Yuechao Li, Kang Lu, Yanjie Wang, Zhiguo Huang, Lihua Liu, Yanhong Wang, Shu Zhao, Xuyun Li, Junnan Yu, Jiahui Xuan, Lina Hou, Yan Sun, Lihua Han, Hui Gao, Fei Yang, Baofeng Zhang, Ying Liu, Shuangshuang Tian, Ye Pan, Zhenwei Du, Zhimin Zhang, Yong
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organization: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University – sequence: 5 givenname: Kang surname: Li fullname: Li, Kang organization: Department of Epidemiology and Biostatistics, Public Health School, Harbin Medical University – sequence: 6 givenname: Shuangshuang surname: Liu fullname: Liu, Shuangshuang organization: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University – sequence: 7 givenname: Yuechao surname: Huang fullname: Huang, Yuechao organization: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University – sequence: 8 givenname: Xuyun surname: Zhao fullname: Zhao, Xuyun organization: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University – sequence: 9 givenname: Lihua surname: Huang fullname: Huang, Lihua organization: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University – sequence: 10 givenname: Zhiguo surname: Wang fullname: Wang, Zhiguo organization: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University – sequence: 11 givenname: Yan surname: Hou fullname: Hou, Yan organization: Department of Epidemiology and Biostatistics, Public Health School, Harbin Medical University – sequence: 12 givenname: Junnan surname: Li fullname: Li, Junnan organization: Department of Epidemiology and Biostatistics, Public Health School, Harbin Medical University – sequence: 13 givenname: Ye surname: Tian fullname: Tian, Ye organization: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Division of Pathophysiology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China and the Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University – sequence: 14 givenname: Jiahui surname: Yu fullname: Yu, Jiahui organization: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University – sequence: 15 givenname: Hui surname: Han fullname: Han, Hui organization: Department of gerontology, the First Affiliated Hospital, Harbin Medical University – sequence: 16 givenname: Yanhong surname: Liu fullname: Liu, Yanhong organization: Laboratories of Medicine, the Second Affiliated Hospital, Harbin Medical University – sequence: 17 givenname: Fei surname: Gao fullname: Gao, Fei organization: Laboratories of Medicine, the Second Affiliated Hospital, Harbin Medical University – sequence: 18 givenname: Yong surname: Zhang fullname: Zhang, Yong organization: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University – sequence: 19 givenname: Shu surname: Wang fullname: Wang, Shu organization: Department of Cardiology, the First Affiliated Hospital, Harbin Medical University – sequence: 20 givenname: Zhimin surname: Du fullname: Du, Zhimin organization: Institute of Clinical Pharmacology, the Second Affiliated Hospital, Harbin Medical University – sequence: 21 givenname: Yanjie surname: Lu fullname: Lu, Yanjie organization: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University – sequence: 22 givenname: Baofeng surname: Yang fullname: Yang, Baofeng organization: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Department of Pharmacology and Therapeutics, Melbourne School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne
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Snippet	This study sought to evaluate the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers for acute myocardial infarction (AMI). We measured the...
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SubjectTerms	38/90 692/4019/592/75/2/1674 692/53/2421 Animals Antisense RNA Biomarkers Biomarkers - blood Blood Cardiac arrhythmia Cardiovascular diseases Complementarity-determining region 1 Disease Models, Animal Heart attacks Humanities and Social Sciences Humans Mice Mice, Inbred C57BL Middle Aged multidisciplinary Myocardial infarction Myocardial Infarction - blood Myocardial Infarction - diagnosis Prognosis RNA, Long Noncoding - blood Rodents Science Zinc finger proteins
Title	Reciprocal Changes of Circulating Long Non-Coding RNAs ZFAS1 and CDR1AS Predict Acute Myocardial Infarction
URI	https://link.springer.com/article/10.1038/srep22384 https://www.ncbi.nlm.nih.gov/pubmed/26928231 https://www.proquest.com/docview/1898704424 https://www.proquest.com/docview/1770221374 https://pubmed.ncbi.nlm.nih.gov/PMC4772828
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