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Several lines of evidence, including our studies, have suggested direct effects of dyslipidemia on cardiac energy metabolism, but details of these effects are not clear. This study aimed to investigate how mild dyslipidemia affects cardiac mitochondria function and vascular nucleotide metabolism. The analyses were performed in 3- and 6-month-old knock-out mice for low-density lipoprotein receptor (Ldlr\u2212\/\u2212) and compared to wild-type C57Bl\/6J mice (WT). Cardiac isolated mitochondria function was analyzed using Seahorse metabolic flux analyzer. The mechanical function of the heart was measured using echocardiography. The levels of fusion, fission, and mitochondrial biogenesis proteins were determined by ELISA kits, while the cardiac intracellular nucleotide concentration and vascular pattern of nucleotide metabolism ecto-enzymes were analyzed using reverse-phase high-performance liquid chromatography. We revealed the downregulation of mitochondrial complex I, together with a decreased activity of citrate synthase (CS), reduced levels of nuclear respiratory factor 1 and mitochondrial fission 1 protein, as well as lower intracellular adenosine and guanosine triphosphates\u2019 pool in the hearts of 6-month Ldlr\u2212\/\u2212 mice vs. age-matched WT. The analysis of vascular ecto-enzyme pattern revealed decreased rate of extracellular adenosine monophosphate hydrolysis and increased ecto-adenosine deaminase activity (eADA) in 6-month Ldlr\u2212\/\u2212 vs. WT mice. No changes were observed in echocardiography parameters in both age groups of Ldlr\u2212\/\u2212 mice. Younger hyperlipidemic mice revealed no differences in cardiac mitochondria function, CS activity, intracellular nucleotides, mitochondrial biogenesis, and dynamics but exhibited minor changes in vascular eADA activity vs. WT. This study revealed that dysfunction of cardiac mitochondria develops during prolonged mild hyperlipidemia at the time point corresponding to the formation of early vascular alterations.<\/jats:p>","DOI":"10.3390\/ijms231911488","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T21:03:10Z","timestamp":1664485390000},"page":"11488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cardiac Mitochondria Dysfunction in Dyslipidemic Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4394-0292","authenticated-orcid":false,"given":"Alicja","family":"Braczko","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, Debinki 1 St., 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3324-9246","authenticated-orcid":false,"given":"Barbara","family":"Kutryb-Zajac","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, Debinki 1 St., 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8219-7497","authenticated-orcid":false,"given":"Agata","family":"Jedrzejewska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, Debinki 1 St., 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5599-0417","authenticated-orcid":false,"given":"Oliwia","family":"Krol","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, Debinki 1 St., 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Mierzejewska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, Debinki 1 St., 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Zabielska-Kaczorowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, Debinki 1 St., 80-211 Gdansk, Poland"},{"name":"Department of Physiology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa M.","family":"Slominska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, Debinki 1 St., 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0190-9414","authenticated-orcid":false,"given":"Ryszard T.","family":"Smolenski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, Debinki 1 St., 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart Disease and Stroke Statistics\u20142021 Update","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1161\/CIRCRESAHA.119.315644","article-title":"Age-Associated Mitochondrial Dysfunction Accelerates Atherogenesis","volume":"126","author":"Tyrrell","year":"2020","journal-title":"Circ. 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