Oral batyl alcohol supplementation rescues decreased cardiac conduction in ether phospholipid‐deficient mice
Plasmalogens (Pls) are a class of membrane phospholipids which serve a number of essential biological functions. Deficiency of Pls is associated with common disorders such as Alzheimer's disease or ischemic heart disease. A complete lack of Pls due to genetically determined defective biosynthes...
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Veröffentlicht in: | Journal of inherited metabolic disease 2020-09, Vol.43 (5), p.1046-1055 |
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creator | Todt, Hannes Dorninger, Fabian Rothauer, Peter J. Fischer, Claus M. Schranz, Michael Bruegger, Britta Lüchtenborg, Christian Ebner, Janine Hilber, Karlheinz Koenig, Xaver Erdem, Fatma A. Gawali, Vaibhavkumar S. Berger, Johannes |
description | Plasmalogens (Pls) are a class of membrane phospholipids which serve a number of essential biological functions. Deficiency of Pls is associated with common disorders such as Alzheimer's disease or ischemic heart disease. A complete lack of Pls due to genetically determined defective biosynthesis gives rise to rhizomelic chondrodysplasia punctata (RCDP), characterized by a number of severe disabling pathologic features and death in early childhood. Frequent cardiac manifestations of RCDP include septal defects, mitral valve prolapse, and patent ductus arteriosus. In a mouse model of RCDP, reduced nerve conduction velocity was partially rescued by dietary oral supplementation of the Pls precursor batyl alcohol (BA). Here, we examine the impact of Pls deficiency on cardiac impulse conduction in a similar mouse model (Gnpat KO). In‐vivo electrocardiographic recordings showed that the duration of the QRS complex was significantly longer in Gnpat KO mice than in age‐ and sex‐matched wild‐type animals, indicative of reduced cardiac conduction velocity. Oral supplementation of BA for 2 months resulted in normalization of cardiac Pls levels and of the QRS duration in Gnpat KO mice but not in untreated animals. BA treatment had no effect on the QRS duration in age‐matched wild‐type mice. These data suggest that Pls deficiency is associated with increased ventricular conduction time which can be rescued by oral BA supplementation. |
doi_str_mv | 10.1002/jimd.12264 |
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Deficiency of Pls is associated with common disorders such as Alzheimer's disease or ischemic heart disease. A complete lack of Pls due to genetically determined defective biosynthesis gives rise to rhizomelic chondrodysplasia punctata (RCDP), characterized by a number of severe disabling pathologic features and death in early childhood. Frequent cardiac manifestations of RCDP include septal defects, mitral valve prolapse, and patent ductus arteriosus. In a mouse model of RCDP, reduced nerve conduction velocity was partially rescued by dietary oral supplementation of the Pls precursor batyl alcohol (BA). Here, we examine the impact of Pls deficiency on cardiac impulse conduction in a similar mouse model (Gnpat KO). In‐vivo electrocardiographic recordings showed that the duration of the QRS complex was significantly longer in Gnpat KO mice than in age‐ and sex‐matched wild‐type animals, indicative of reduced cardiac conduction velocity. Oral supplementation of BA for 2 months resulted in normalization of cardiac Pls levels and of the QRS duration in Gnpat KO mice but not in untreated animals. BA treatment had no effect on the QRS duration in age‐matched wild‐type mice. These data suggest that Pls deficiency is associated with increased ventricular conduction time which can be rescued by oral BA supplementation.</description><identifier>ISSN: 0141-8955</identifier><identifier>EISSN: 1573-2665</identifier><identifier>DOI: 10.1002/jimd.12264</identifier><identifier>PMID: 32441337</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Alzheimer's disease ; arrhythmia ; batyl alcohol ; cardiac impulse conduction ; Children ; Chondrodystrophy ; Coronary artery disease ; Dietary supplements ; electrocardiography ; Heart diseases ; Ischemia ; Mitral valve ; Nerve conduction ; Neurodegenerative diseases ; Original ; Phospholipids ; Plasmalogens ; Rheumatic heart disease ; rhizomelic chondrodysplasia punctata ; Velocity ; Ventricle</subject><ispartof>Journal of inherited metabolic disease, 2020-09, Vol.43 (5), p.1046-1055</ispartof><rights>2020 The Authors. published by John Wiley & Sons Ltd on behalf of SSIEM</rights><rights>2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5144-ed33ebf9b13f8b2e950093e6bae1a7812fd2093354841ebafe0ff66e329bb0ea3</citedby><cites>FETCH-LOGICAL-c5144-ed33ebf9b13f8b2e950093e6bae1a7812fd2093354841ebafe0ff66e329bb0ea3</cites><orcidid>0000-0002-1147-4370</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjimd.12264$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjimd.12264$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32441337$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Todt, Hannes</creatorcontrib><creatorcontrib>Dorninger, Fabian</creatorcontrib><creatorcontrib>Rothauer, Peter J.</creatorcontrib><creatorcontrib>Fischer, Claus M.</creatorcontrib><creatorcontrib>Schranz, Michael</creatorcontrib><creatorcontrib>Bruegger, Britta</creatorcontrib><creatorcontrib>Lüchtenborg, Christian</creatorcontrib><creatorcontrib>Ebner, Janine</creatorcontrib><creatorcontrib>Hilber, Karlheinz</creatorcontrib><creatorcontrib>Koenig, Xaver</creatorcontrib><creatorcontrib>Erdem, Fatma A.</creatorcontrib><creatorcontrib>Gawali, Vaibhavkumar S.</creatorcontrib><creatorcontrib>Berger, Johannes</creatorcontrib><title>Oral batyl alcohol supplementation rescues decreased cardiac conduction in ether phospholipid‐deficient mice</title><title>Journal of inherited metabolic disease</title><addtitle>J Inherit Metab Dis</addtitle><description>Plasmalogens (Pls) are a class of membrane phospholipids which serve a number of essential biological functions. Deficiency of Pls is associated with common disorders such as Alzheimer's disease or ischemic heart disease. A complete lack of Pls due to genetically determined defective biosynthesis gives rise to rhizomelic chondrodysplasia punctata (RCDP), characterized by a number of severe disabling pathologic features and death in early childhood. Frequent cardiac manifestations of RCDP include septal defects, mitral valve prolapse, and patent ductus arteriosus. In a mouse model of RCDP, reduced nerve conduction velocity was partially rescued by dietary oral supplementation of the Pls precursor batyl alcohol (BA). Here, we examine the impact of Pls deficiency on cardiac impulse conduction in a similar mouse model (Gnpat KO). In‐vivo electrocardiographic recordings showed that the duration of the QRS complex was significantly longer in Gnpat KO mice than in age‐ and sex‐matched wild‐type animals, indicative of reduced cardiac conduction velocity. Oral supplementation of BA for 2 months resulted in normalization of cardiac Pls levels and of the QRS duration in Gnpat KO mice but not in untreated animals. BA treatment had no effect on the QRS duration in age‐matched wild‐type mice. These data suggest that Pls deficiency is associated with increased ventricular conduction time which can be rescued by oral BA supplementation.</description><subject>Alzheimer's disease</subject><subject>arrhythmia</subject><subject>batyl alcohol</subject><subject>cardiac impulse conduction</subject><subject>Children</subject><subject>Chondrodystrophy</subject><subject>Coronary artery disease</subject><subject>Dietary supplements</subject><subject>electrocardiography</subject><subject>Heart diseases</subject><subject>Ischemia</subject><subject>Mitral valve</subject><subject>Nerve conduction</subject><subject>Neurodegenerative diseases</subject><subject>Original</subject><subject>Phospholipids</subject><subject>Plasmalogens</subject><subject>Rheumatic heart disease</subject><subject>rhizomelic chondrodysplasia punctata</subject><subject>Velocity</subject><subject>Ventricle</subject><issn>0141-8955</issn><issn>1573-2665</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp9kc1qFTEYhoNY7LG68QIk4EYKU_N_ZjZCqVUrlW50HTLJF08OmcmYzChn5yV4jV6JaU9b1IWEEEgennwvL0LPKDmhhLBX2zC4E8qYEg_Qiso1b5hS8iFaESpo03ZSHqLHpWwJIV0r5SN0yJkQlPP1Co1X2UTcm3kXsYk2bVLEZZmmCAOMs5lDGnGGYhco2IHNYAo4bE12wVhs0-gWewOFEcO8gYynTSp1xzAF9-vHTwc-2FBdeAgWnqADb2KBp7fnEfr89vzT2fvm8urdxdnpZWMlFaIBxzn0vusp923PoJN1dA6qN0DNuqXMO1YvuBStoNAbD8R7pYCzru8JGH6EXu-909IP4Gz9v-bUUw6DyTudTNB_v4xho7-kb3otBamrCl7eCnL6WsPPegjFQoxmhLQUzQRRnLRKthV98Q-6TUsea7xKCcEUo1xV6nhP2ZxKyeDvh6FEX9eor2vUNzVW-Pmf49-jd71VgO6B7yHC7j8q_eHi45u99Dd4dKw1</recordid><startdate>202009</startdate><enddate>202009</enddate><creator>Todt, Hannes</creator><creator>Dorninger, Fabian</creator><creator>Rothauer, Peter J.</creator><creator>Fischer, Claus M.</creator><creator>Schranz, Michael</creator><creator>Bruegger, Britta</creator><creator>Lüchtenborg, Christian</creator><creator>Ebner, Janine</creator><creator>Hilber, Karlheinz</creator><creator>Koenig, Xaver</creator><creator>Erdem, Fatma A.</creator><creator>Gawali, Vaibhavkumar S.</creator><creator>Berger, Johannes</creator><general>John Wiley & Sons, Inc</general><general>Blackwell Publishing Ltd</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1147-4370</orcidid></search><sort><creationdate>202009</creationdate><title>Oral batyl alcohol supplementation rescues decreased cardiac conduction in ether phospholipid‐deficient mice</title><author>Todt, Hannes ; Dorninger, Fabian ; Rothauer, Peter J. ; Fischer, Claus M. ; Schranz, Michael ; Bruegger, Britta ; Lüchtenborg, Christian ; Ebner, Janine ; Hilber, Karlheinz ; Koenig, Xaver ; Erdem, Fatma A. ; Gawali, Vaibhavkumar S. ; Berger, Johannes</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5144-ed33ebf9b13f8b2e950093e6bae1a7812fd2093354841ebafe0ff66e329bb0ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alzheimer's disease</topic><topic>arrhythmia</topic><topic>batyl alcohol</topic><topic>cardiac impulse conduction</topic><topic>Children</topic><topic>Chondrodystrophy</topic><topic>Coronary artery disease</topic><topic>Dietary supplements</topic><topic>electrocardiography</topic><topic>Heart diseases</topic><topic>Ischemia</topic><topic>Mitral valve</topic><topic>Nerve conduction</topic><topic>Neurodegenerative diseases</topic><topic>Original</topic><topic>Phospholipids</topic><topic>Plasmalogens</topic><topic>Rheumatic heart disease</topic><topic>rhizomelic chondrodysplasia punctata</topic><topic>Velocity</topic><topic>Ventricle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Todt, Hannes</creatorcontrib><creatorcontrib>Dorninger, Fabian</creatorcontrib><creatorcontrib>Rothauer, Peter J.</creatorcontrib><creatorcontrib>Fischer, Claus M.</creatorcontrib><creatorcontrib>Schranz, Michael</creatorcontrib><creatorcontrib>Bruegger, Britta</creatorcontrib><creatorcontrib>Lüchtenborg, Christian</creatorcontrib><creatorcontrib>Ebner, Janine</creatorcontrib><creatorcontrib>Hilber, Karlheinz</creatorcontrib><creatorcontrib>Koenig, Xaver</creatorcontrib><creatorcontrib>Erdem, Fatma A.</creatorcontrib><creatorcontrib>Gawali, Vaibhavkumar S.</creatorcontrib><creatorcontrib>Berger, Johannes</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of inherited metabolic disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Todt, Hannes</au><au>Dorninger, Fabian</au><au>Rothauer, Peter J.</au><au>Fischer, Claus M.</au><au>Schranz, Michael</au><au>Bruegger, Britta</au><au>Lüchtenborg, Christian</au><au>Ebner, Janine</au><au>Hilber, Karlheinz</au><au>Koenig, Xaver</au><au>Erdem, Fatma A.</au><au>Gawali, Vaibhavkumar S.</au><au>Berger, Johannes</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oral batyl alcohol supplementation rescues decreased cardiac conduction in ether phospholipid‐deficient mice</atitle><jtitle>Journal of inherited metabolic disease</jtitle><addtitle>J Inherit Metab Dis</addtitle><date>2020-09</date><risdate>2020</risdate><volume>43</volume><issue>5</issue><spage>1046</spage><epage>1055</epage><pages>1046-1055</pages><issn>0141-8955</issn><eissn>1573-2665</eissn><abstract>Plasmalogens (Pls) are a class of membrane phospholipids which serve a number of essential biological functions. 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Oral supplementation of BA for 2 months resulted in normalization of cardiac Pls levels and of the QRS duration in Gnpat KO mice but not in untreated animals. BA treatment had no effect on the QRS duration in age‐matched wild‐type mice. These data suggest that Pls deficiency is associated with increased ventricular conduction time which can be rescued by oral BA supplementation.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>32441337</pmid><doi>10.1002/jimd.12264</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1147-4370</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Alzheimer's disease arrhythmia batyl alcohol cardiac impulse conduction Children Chondrodystrophy Coronary artery disease Dietary supplements electrocardiography Heart diseases Ischemia Mitral valve Nerve conduction Neurodegenerative diseases Original Phospholipids Plasmalogens Rheumatic heart disease rhizomelic chondrodysplasia punctata Velocity Ventricle |
title | Oral batyl alcohol supplementation rescues decreased cardiac conduction in ether phospholipid‐deficient mice |
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