Circulating MicroRNA-125b Predicts the Presence and Progression of Uremic Vascular Calcification
OBJECTIVE—Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand. APPROACH AND RESULTS—We identified circulating, cell-free microRNAs as potential biomarkers using in vitro VC models...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2017-07, Vol.37 (7), p.1402-1414 |
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| creator | Chao, Chia-Ter Liu, You-Pi Su, Sheng-Fang Yeh, Hsiang-Yuan Chen, Hsuan-Yu Lee, Pei-Jung Chen, Wan-Jiun Lee, Yee-Ming Huang, Jenq-Wen Chiang, Chih-Kang Hung, Kuan-Yu Chen, Huei-Wen |
| description | OBJECTIVE—Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand.
APPROACH AND RESULTS—We identified circulating, cell-free microRNAs as potential biomarkers using in vitro VC models in which both rat and human aortic vascular smooth muscle cells were treated with high levels of phosphate to mimic uremic hyperphosphatemia. Using an Affymetrix microRNA array, we found that miR-125b and miR-382 expression levels declined significantly as biomineralization progressed, but this decline was only observed for miR-125b in the culture medium. A time-dependent decrease in aortic tissue and serum miR-125b levels was also found in both ex vivo and in vivo renal failure models. We examined the levels of circulating, cell-free miR-125b in sera from patients with end-stage renal diseases (n=88) and found an inverse association between the severity of VC and the circulating miR-125b level, irrespective of age or mineral-related hormones (odds ratio, 0.71; P=0.03). Furthermore, serum miR-125b levels on enrollment can predict VC progression years later (for high versus low, odds ratio, 0.14; P |
| doi_str_mv | 10.1161/ATVBAHA.117.309566 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1161_ATVBAHA_117_309566</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>28522697</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4606-2360f4e98f47e3d642db6ca810ec0b760e3aa194ceb82740868d4eca04887e363</originalsourceid><addsrcrecordid>eNp9kM1OwzAQhC0EoqXwAhyQXyDFdhzHOYYIKFL5EWp7DY6zaQ1pUtmJKt4eVykcOe1-0sxodxC6pmRKqaC36WJ1l85SD_E0JEkkxAka04jxgItQnPqdxEkQCc5G6MK5T0IIZ4ycoxGTEWMiicfoIzNW97XqTLPGz0bb9v0lDSiLCvxmoTS6c7jbwAEcNBqwakoP7dqzM22D2wovLWyNxivlDkkWZ6rWpjLah7bNJTqrVO3g6jgnaPlwv8hmwfz18SlL54HmgoiAhYJUHBJZ8RjC0t9cFkIrSQloUsSCQKgUTbiGQrKYEylkyUErwqX0BhFOEBty_QvOWajynTVbZb9zSvJDXfmxLg9xPtTlTTeDadcXWyj_LL_9eIEYBPu27sC6r7rfg803oOpu81_yD4Rud1Y</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Circulating MicroRNA-125b Predicts the Presence and Progression of Uremic Vascular Calcification</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><source>Alma/SFX Local Collection</source><creator>Chao, Chia-Ter ; Liu, You-Pi ; Su, Sheng-Fang ; Yeh, Hsiang-Yuan ; Chen, Hsuan-Yu ; Lee, Pei-Jung ; Chen, Wan-Jiun ; Lee, Yee-Ming ; Huang, Jenq-Wen ; Chiang, Chih-Kang ; Hung, Kuan-Yu ; Chen, Huei-Wen</creator><creatorcontrib>Chao, Chia-Ter ; Liu, You-Pi ; Su, Sheng-Fang ; Yeh, Hsiang-Yuan ; Chen, Hsuan-Yu ; Lee, Pei-Jung ; Chen, Wan-Jiun ; Lee, Yee-Ming ; Huang, Jenq-Wen ; Chiang, Chih-Kang ; Hung, Kuan-Yu ; Chen, Huei-Wen</creatorcontrib><description>OBJECTIVE—Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand.
APPROACH AND RESULTS—We identified circulating, cell-free microRNAs as potential biomarkers using in vitro VC models in which both rat and human aortic vascular smooth muscle cells were treated with high levels of phosphate to mimic uremic hyperphosphatemia. Using an Affymetrix microRNA array, we found that miR-125b and miR-382 expression levels declined significantly as biomineralization progressed, but this decline was only observed for miR-125b in the culture medium. A time-dependent decrease in aortic tissue and serum miR-125b levels was also found in both ex vivo and in vivo renal failure models. We examined the levels of circulating, cell-free miR-125b in sera from patients with end-stage renal diseases (n=88) and found an inverse association between the severity of VC and the circulating miR-125b level, irrespective of age or mineral-related hormones (odds ratio, 0.71; P=0.03). Furthermore, serum miR-125b levels on enrollment can predict VC progression years later (for high versus low, odds ratio, 0.14; P<0.01; for the highest versus lowest tertile and middle versus lowest tertile, odds ratio, 0.55 and 0.13; P=0.3 and <0.01, respectively). The uremic VC prediction efficacy using circulating miR-125b levels was also observed in an independent cohort (n=135).
CONCLUSIONS—The results suggest that serum miR-125b levels are associated with VC severity and serve as a novel predictive marker for the risk of uremia-associated calcification progression.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.117.309566</identifier><identifier>PMID: 28522697</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Aged ; Aged, 80 and over ; Animals ; Aorta, Thoracic - metabolism ; Aorta, Thoracic - pathology ; Aortic Diseases - blood ; Aortic Diseases - etiology ; Aortic Diseases - genetics ; Aortic Diseases - pathology ; Apoptosis ; Cells, Cultured ; Chi-Square Distribution ; Disease Models, Animal ; Disease Progression ; Down-Regulation ; Female ; Genetic Markers ; Humans ; Hyperphosphatemia - blood ; Hyperphosphatemia - etiology ; Hyperphosphatemia - genetics ; Kaplan-Meier Estimate ; Kidney Failure, Chronic - blood ; Kidney Failure, Chronic - etiology ; Kidney Failure, Chronic - genetics ; Logistic Models ; Male ; MicroRNAs - blood ; MicroRNAs - genetics ; Middle Aged ; Multivariate Analysis ; Muscle, Smooth, Vascular - metabolism ; Muscle, Smooth, Vascular - pathology ; Myocytes, Smooth Muscle - metabolism ; Myocytes, Smooth Muscle - pathology ; Odds Ratio ; Predictive Value of Tests ; Rats, Sprague-Dawley ; Risk Factors ; Severity of Illness Index ; Time Factors ; Transfection ; Uremia - blood ; Uremia - complications ; Uremia - etiology ; Uremia - genetics ; Vascular Calcification - blood ; Vascular Calcification - etiology ; Vascular Calcification - genetics ; Vascular Calcification - pathology</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2017-07, Vol.37 (7), p.1402-1414</ispartof><rights>2017 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4606-2360f4e98f47e3d642db6ca810ec0b760e3aa194ceb82740868d4eca04887e363</citedby><cites>FETCH-LOGICAL-c4606-2360f4e98f47e3d642db6ca810ec0b760e3aa194ceb82740868d4eca04887e363</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28522697$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chao, Chia-Ter</creatorcontrib><creatorcontrib>Liu, You-Pi</creatorcontrib><creatorcontrib>Su, Sheng-Fang</creatorcontrib><creatorcontrib>Yeh, Hsiang-Yuan</creatorcontrib><creatorcontrib>Chen, Hsuan-Yu</creatorcontrib><creatorcontrib>Lee, Pei-Jung</creatorcontrib><creatorcontrib>Chen, Wan-Jiun</creatorcontrib><creatorcontrib>Lee, Yee-Ming</creatorcontrib><creatorcontrib>Huang, Jenq-Wen</creatorcontrib><creatorcontrib>Chiang, Chih-Kang</creatorcontrib><creatorcontrib>Hung, Kuan-Yu</creatorcontrib><creatorcontrib>Chen, Huei-Wen</creatorcontrib><title>Circulating MicroRNA-125b Predicts the Presence and Progression of Uremic Vascular Calcification</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVE—Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand.
APPROACH AND RESULTS—We identified circulating, cell-free microRNAs as potential biomarkers using in vitro VC models in which both rat and human aortic vascular smooth muscle cells were treated with high levels of phosphate to mimic uremic hyperphosphatemia. Using an Affymetrix microRNA array, we found that miR-125b and miR-382 expression levels declined significantly as biomineralization progressed, but this decline was only observed for miR-125b in the culture medium. A time-dependent decrease in aortic tissue and serum miR-125b levels was also found in both ex vivo and in vivo renal failure models. We examined the levels of circulating, cell-free miR-125b in sera from patients with end-stage renal diseases (n=88) and found an inverse association between the severity of VC and the circulating miR-125b level, irrespective of age or mineral-related hormones (odds ratio, 0.71; P=0.03). Furthermore, serum miR-125b levels on enrollment can predict VC progression years later (for high versus low, odds ratio, 0.14; P<0.01; for the highest versus lowest tertile and middle versus lowest tertile, odds ratio, 0.55 and 0.13; P=0.3 and <0.01, respectively). The uremic VC prediction efficacy using circulating miR-125b levels was also observed in an independent cohort (n=135).
CONCLUSIONS—The results suggest that serum miR-125b levels are associated with VC severity and serve as a novel predictive marker for the risk of uremia-associated calcification progression.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Animals</subject><subject>Aorta, Thoracic - metabolism</subject><subject>Aorta, Thoracic - pathology</subject><subject>Aortic Diseases - blood</subject><subject>Aortic Diseases - etiology</subject><subject>Aortic Diseases - genetics</subject><subject>Aortic Diseases - pathology</subject><subject>Apoptosis</subject><subject>Cells, Cultured</subject><subject>Chi-Square Distribution</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Down-Regulation</subject><subject>Female</subject><subject>Genetic Markers</subject><subject>Humans</subject><subject>Hyperphosphatemia - blood</subject><subject>Hyperphosphatemia - etiology</subject><subject>Hyperphosphatemia - genetics</subject><subject>Kaplan-Meier Estimate</subject><subject>Kidney Failure, Chronic - blood</subject><subject>Kidney Failure, Chronic - etiology</subject><subject>Kidney Failure, Chronic - genetics</subject><subject>Logistic Models</subject><subject>Male</subject><subject>MicroRNAs - blood</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Myocytes, Smooth Muscle - pathology</subject><subject>Odds Ratio</subject><subject>Predictive Value of Tests</subject><subject>Rats, Sprague-Dawley</subject><subject>Risk Factors</subject><subject>Severity of Illness Index</subject><subject>Time Factors</subject><subject>Transfection</subject><subject>Uremia - blood</subject><subject>Uremia - complications</subject><subject>Uremia - etiology</subject><subject>Uremia - genetics</subject><subject>Vascular Calcification - blood</subject><subject>Vascular Calcification - etiology</subject><subject>Vascular Calcification - genetics</subject><subject>Vascular Calcification - pathology</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1OwzAQhC0EoqXwAhyQXyDFdhzHOYYIKFL5EWp7DY6zaQ1pUtmJKt4eVykcOe1-0sxodxC6pmRKqaC36WJ1l85SD_E0JEkkxAka04jxgItQnPqdxEkQCc5G6MK5T0IIZ4ycoxGTEWMiicfoIzNW97XqTLPGz0bb9v0lDSiLCvxmoTS6c7jbwAEcNBqwakoP7dqzM22D2wovLWyNxivlDkkWZ6rWpjLah7bNJTqrVO3g6jgnaPlwv8hmwfz18SlL54HmgoiAhYJUHBJZ8RjC0t9cFkIrSQloUsSCQKgUTbiGQrKYEylkyUErwqX0BhFOEBty_QvOWajynTVbZb9zSvJDXfmxLg9xPtTlTTeDadcXWyj_LL_9eIEYBPu27sC6r7rfg803oOpu81_yD4Rud1Y</recordid><startdate>201707</startdate><enddate>201707</enddate><creator>Chao, Chia-Ter</creator><creator>Liu, You-Pi</creator><creator>Su, Sheng-Fang</creator><creator>Yeh, Hsiang-Yuan</creator><creator>Chen, Hsuan-Yu</creator><creator>Lee, Pei-Jung</creator><creator>Chen, Wan-Jiun</creator><creator>Lee, Yee-Ming</creator><creator>Huang, Jenq-Wen</creator><creator>Chiang, Chih-Kang</creator><creator>Hung, Kuan-Yu</creator><creator>Chen, Huei-Wen</creator><general>American Heart Association, Inc</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></search><sort><creationdate>201707</creationdate><title>Circulating MicroRNA-125b Predicts the Presence and Progression of Uremic Vascular Calcification</title><author>Chao, Chia-Ter ; Liu, You-Pi ; Su, Sheng-Fang ; Yeh, Hsiang-Yuan ; Chen, Hsuan-Yu ; Lee, Pei-Jung ; Chen, Wan-Jiun ; Lee, Yee-Ming ; Huang, Jenq-Wen ; Chiang, Chih-Kang ; Hung, Kuan-Yu ; Chen, Huei-Wen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4606-2360f4e98f47e3d642db6ca810ec0b760e3aa194ceb82740868d4eca04887e363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Animals</topic><topic>Aorta, Thoracic - metabolism</topic><topic>Aorta, Thoracic - pathology</topic><topic>Aortic Diseases - blood</topic><topic>Aortic Diseases - etiology</topic><topic>Aortic Diseases - genetics</topic><topic>Aortic Diseases - pathology</topic><topic>Apoptosis</topic><topic>Cells, Cultured</topic><topic>Chi-Square Distribution</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Genetic Markers</topic><topic>Humans</topic><topic>Hyperphosphatemia - blood</topic><topic>Hyperphosphatemia - etiology</topic><topic>Hyperphosphatemia - genetics</topic><topic>Kaplan-Meier Estimate</topic><topic>Kidney Failure, Chronic - blood</topic><topic>Kidney Failure, Chronic - etiology</topic><topic>Kidney Failure, Chronic - genetics</topic><topic>Logistic Models</topic><topic>Male</topic><topic>MicroRNAs - blood</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Muscle, Smooth, Vascular - pathology</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Myocytes, Smooth Muscle - pathology</topic><topic>Odds Ratio</topic><topic>Predictive Value of Tests</topic><topic>Rats, Sprague-Dawley</topic><topic>Risk Factors</topic><topic>Severity of Illness Index</topic><topic>Time Factors</topic><topic>Transfection</topic><topic>Uremia - blood</topic><topic>Uremia - complications</topic><topic>Uremia - etiology</topic><topic>Uremia - genetics</topic><topic>Vascular Calcification - blood</topic><topic>Vascular Calcification - etiology</topic><topic>Vascular Calcification - genetics</topic><topic>Vascular Calcification - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chao, Chia-Ter</creatorcontrib><creatorcontrib>Liu, You-Pi</creatorcontrib><creatorcontrib>Su, Sheng-Fang</creatorcontrib><creatorcontrib>Yeh, Hsiang-Yuan</creatorcontrib><creatorcontrib>Chen, Hsuan-Yu</creatorcontrib><creatorcontrib>Lee, Pei-Jung</creatorcontrib><creatorcontrib>Chen, Wan-Jiun</creatorcontrib><creatorcontrib>Lee, Yee-Ming</creatorcontrib><creatorcontrib>Huang, Jenq-Wen</creatorcontrib><creatorcontrib>Chiang, Chih-Kang</creatorcontrib><creatorcontrib>Hung, Kuan-Yu</creatorcontrib><creatorcontrib>Chen, Huei-Wen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chao, Chia-Ter</au><au>Liu, You-Pi</au><au>Su, Sheng-Fang</au><au>Yeh, Hsiang-Yuan</au><au>Chen, Hsuan-Yu</au><au>Lee, Pei-Jung</au><au>Chen, Wan-Jiun</au><au>Lee, Yee-Ming</au><au>Huang, Jenq-Wen</au><au>Chiang, Chih-Kang</au><au>Hung, Kuan-Yu</au><au>Chen, Huei-Wen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating MicroRNA-125b Predicts the Presence and Progression of Uremic Vascular Calcification</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2017-07</date><risdate>2017</risdate><volume>37</volume><issue>7</issue><spage>1402</spage><epage>1414</epage><pages>1402-1414</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><abstract>OBJECTIVE—Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand.
APPROACH AND RESULTS—We identified circulating, cell-free microRNAs as potential biomarkers using in vitro VC models in which both rat and human aortic vascular smooth muscle cells were treated with high levels of phosphate to mimic uremic hyperphosphatemia. Using an Affymetrix microRNA array, we found that miR-125b and miR-382 expression levels declined significantly as biomineralization progressed, but this decline was only observed for miR-125b in the culture medium. A time-dependent decrease in aortic tissue and serum miR-125b levels was also found in both ex vivo and in vivo renal failure models. We examined the levels of circulating, cell-free miR-125b in sera from patients with end-stage renal diseases (n=88) and found an inverse association between the severity of VC and the circulating miR-125b level, irrespective of age or mineral-related hormones (odds ratio, 0.71; P=0.03). Furthermore, serum miR-125b levels on enrollment can predict VC progression years later (for high versus low, odds ratio, 0.14; P<0.01; for the highest versus lowest tertile and middle versus lowest tertile, odds ratio, 0.55 and 0.13; P=0.3 and <0.01, respectively). The uremic VC prediction efficacy using circulating miR-125b levels was also observed in an independent cohort (n=135).
CONCLUSIONS—The results suggest that serum miR-125b levels are associated with VC severity and serve as a novel predictive marker for the risk of uremia-associated calcification progression.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>28522697</pmid><doi>10.1161/ATVBAHA.117.309566</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2017-07, Vol.37 (7), p.1402-1414 |
| issn | 1079-5642 1524-4636 |
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| source | MEDLINE; Journals@Ovid Complete; Alma/SFX Local Collection |
| subjects | Aged Aged, 80 and over Animals Aorta, Thoracic - metabolism Aorta, Thoracic - pathology Aortic Diseases - blood Aortic Diseases - etiology Aortic Diseases - genetics Aortic Diseases - pathology Apoptosis Cells, Cultured Chi-Square Distribution Disease Models, Animal Disease Progression Down-Regulation Female Genetic Markers Humans Hyperphosphatemia - blood Hyperphosphatemia - etiology Hyperphosphatemia - genetics Kaplan-Meier Estimate Kidney Failure, Chronic - blood Kidney Failure, Chronic - etiology Kidney Failure, Chronic - genetics Logistic Models Male MicroRNAs - blood MicroRNAs - genetics Middle Aged Multivariate Analysis Muscle, Smooth, Vascular - metabolism Muscle, Smooth, Vascular - pathology Myocytes, Smooth Muscle - metabolism Myocytes, Smooth Muscle - pathology Odds Ratio Predictive Value of Tests Rats, Sprague-Dawley Risk Factors Severity of Illness Index Time Factors Transfection Uremia - blood Uremia - complications Uremia - etiology Uremia - genetics Vascular Calcification - blood Vascular Calcification - etiology Vascular Calcification - genetics Vascular Calcification - pathology |
| title | Circulating MicroRNA-125b Predicts the Presence and Progression of Uremic Vascular Calcification |
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