Low cardiac content of long-chain acylcarnitines in TMLHE knockout mice prevents ischaemia-reperfusion-induced mitochondrial and cardiac damage

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dc.contributor.authorLiepinsh, Edgars
dc.contributor.authorKuka, Janis
dc.contributor.authorVilks, Karlis
dc.contributor.authorSvalbe, Baiba
dc.contributor.authorStelfa, Gundega
dc.contributor.authorVilskersts, Reinis
dc.contributor.authorSevostjanovs, Eduards
dc.contributor.authorGoldins, Niks Ricards
dc.contributor.authorGroma, Valerija
dc.contributor.authorGrinberga, Solveiga
dc.contributor.authorPlaas, Mario
dc.contributor.authorMakrecka-Kuka, Marina
dc.contributor.authorDambrova, Maija
dc.contributor.institutionRīga Stradiņš University
dc.date.accessioned2021-11-11T07:45:01Z
dc.date.available2021-11-11T07:45:01Z
dc.date.issued2021-12
dc.descriptionCopyright © 2021. Published by Elsevier Inc.
dc.description.abstractIncreased tissue content of long-chain acylcarnitines may induce mitochondrial and cardiac damage by stimulating ROS production. N6-trimethyllysine dioxygenase (TMLD) is the first enzyme in the carnitine/acylcarnitine biosynthesis pathway. Inactivation of the TMLHE gene (TMLHE KO) in mice is expected to limit long-chain acylcarnitine synthesis and thus induce a cardio- and mitochondria-protective phenotype. TMLHE gene deletion in male mice lowered acylcarnitine concentrations in blood and cardiac tissues by up to 85% and decreased fatty acid oxidation by 30% but did not affect muscle and heart function in mice. Metabolome profile analysis revealed increased levels of polyunsaturated fatty acids (PUFAs) and a global shift in fatty acid content from saturated to unsaturated lipids. In the risk area of ischemic hearts in TMLHE KO mouse, the OXPHOS-dependent respiration rate and OXPHOS coupling efficiency were fully preserved. Additionally, the decreased long-chain acylcarnitine synthesis rate in TMLHE KO mice prevented ischaemia-reperfusion-induced ROS production in cardiac mitochondria. This was associated with a 39% smaller infarct size in the TMLHE KO mice. The arrest of the acylcarnitine biosynthesis pathway in TMLHE KO mice prevents ischaemia-reperfusion-induced damage in cardiac mitochondria and decreases infarct size. These results confirm that the decreased accumulation of ROS-increasing fatty acid metabolism intermediates prevents mitochondrial and cardiac damage during ischaemia-reperfusion.en
dc.description.statusPeer reviewed
dc.format.extent5009208
dc.identifier.citationLiepinsh, E, Kuka, J, Vilks, K, Svalbe, B, Stelfa, G, Vilskersts, R, Sevostjanovs, E, Goldins, N R, Groma, V, Grinberga, S, Plaas, M, Makrecka-Kuka, M & Dambrova, M 2021, 'Low cardiac content of long-chain acylcarnitines in TMLHE knockout mice prevents ischaemia-reperfusion-induced mitochondrial and cardiac damage', Free Radical Biology and Medicine, vol. 177, pp. 370-380. https://doi.org/10.1016/j.freeradbiomed.2021.10.035
dc.identifier.doi10.1016/j.freeradbiomed.2021.10.035
dc.identifier.issn0891-5849
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/6815
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85118848478&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofFree Radical Biology and Medicine
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject3.1 Basic medicine
dc.subject1.6 Biological sciences
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.titleLow cardiac content of long-chain acylcarnitines in TMLHE knockout mice prevents ischaemia-reperfusion-induced mitochondrial and cardiac damageen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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