Liepinsh, EdgarsKuka, JanisVilks, KarlisSvalbe, BaibaStelfa, GundegaVilskersts, ReinisSevostjanovs, EduardsGoldins, Niks RicardsGroma, ValerijaGrinberga, SolveigaPlaas, MarioMakrecka-Kuka, MarinaDambrova, Maija2021-11-112021-11-112021-12Liepinsh, 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.2021.10.0350891-5849https://dspace.rsu.lv/jspui/handle/123456789/6815Copyright © 2021. Published by Elsevier Inc.Increased 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.5009208enginfo:eu-repo/semantics/openAccess3.1 Basic medicine1.6 Biological sciences1.1. Scientific article indexed in Web of Science and/or Scopus database/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article10.1016/j.freeradbiomed.2021.10.035http://www.scopus.com/inward/record.url?scp=85118848478&partnerID=8YFLogxK