Myocardial inflammation is associated with impaired mitochondrial oxidative capacity in ischaemic cardiomyopathy
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| Názov: | Myocardial inflammation is associated with impaired mitochondrial oxidative capacity in ischaemic cardiomyopathy |
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| Autori: | Julius Borger, Elric Zweck, Constanze Moos, Patrick Horn, Fabian Voß, Heinz‐Peter Schultheiss, Jacob Eifer Møller, Udo Boeken, Hug Aubin, Artur Lichtenberg, Malte Kelm, Michael Roden, Amin Polzin, Ralf Westenfeld, Julia Szendroedi, Daniel Scheiber |
| Zdroj: | ESC Heart Fail ESC Heart Failure, Vol 12, Iss 2, Pp 1246-1255 (2025) |
| Informácie o vydavateľovi: | Wiley, 2024. |
| Rok vydania: | 2024 |
| Predmety: | Male, Inflammation, Myocardium/metabolism, Heart/metabolism, Inflammation/metabolism, Oxidative Stress/physiology, Heart failure, Middle Aged, Energy Metabolism/physiology, Myocardial Ischemia/metabolism, Mitochondria, Myocarditis/metabolism, RC666-701, Humans, Diseases of the circulatory (Cardiovascular) system, Female, Original Article, Reactive oxygen species, Follow-Up Studies |
| Popis: | AimsMyocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown. We aimed at establishing a relevant role of cardiac inflammation in the impairment of mitochondrial energy production in advanced ischaemic and non‐ischaemic HF.MethodsWe included 81 patients with stage D HF (ICM, n = 44; DCM, n = 37) undergoing left ventricular assist device implantation (n = 59) or heart transplantation (n = 22) and obtained left ventricular tissue samples during open heart surgery. We quantified mitochondrial oxidative capacity, citrate synthase activity (CSA) and fibrosis and lymphocytic infiltration. We considered infiltration of >14 CD3+ cells/mm2 relevant inflammation.ResultsPatients with ICM or DCM did not differ regarding age (61.5 ± 5.7 vs. 56.5 ± 12.7 years, P = 0.164), sex (86% vs. 84% male, P = 0.725), type 2 diabetes mellitus (34% vs. 18%, P = 0.126) or chronic kidney disease (8% vs. 11%, P = 0.994). ICM exhibited oxidative capacity reduced by 23% compared to DCM (108.6 ± 41.4 vs. 141.9 ± 59.9 pmol/(s*mg), P = 0.006). Maximum production of reactive oxygen species was not significantly different between ICM and DCM (0.59 ± 0.28 vs. 0.69 ± 0.36 pmol/(s*ml), P = 0.196). Mitochondrial content, detected by CSA, was lower in ICM (359.6 ± 164.1 vs. 503.0 ± 198.5 nmol/min/mg protein, P = 0.002). Notably, relevant inflammation was more common in ICM (27% vs. 6%, P = 0.024), and the absolute number of infiltrating leucocytes correlated with lower oxidative capacity (r = −0.296, P = 0.019). Fibrosis was more prevalent in ICM (20.9 ± 21.2 vs. 7.2 ± 5.6% of area, P = 0.002), but not associated with oxidative capacity (r = −0.13, P = 0.327).ConclusionsMore than every fourth ICM patient with advanced HF displays myocardial inflammation in the range of inflammatory cardiomyopathy associated with reduced mitochondrial oxidative capacity. Future studies may evaluate inflammation in ICM at earlier stages in standardised fashion to explore the therapeutic potential of immunosuppression to influence trajectories of HF in ICM. |
| Druh dokumentu: | Article Other literature type |
| Jazyk: | English |
| ISSN: | 2055-5822 |
| DOI: | 10.1002/ehf2.15133 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/39477690 https://doaj.org/article/f5c767046c1f44b48c0becbb935eb316 https://portal.findresearcher.sdu.dk/da/publications/e2dc14fc-a6d8-4d93-9077-56e9001aceb2 https://doi.org/10.1002/ehf2.15133 |
| Rights: | CC BY NC ND URL: http://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
| Prístupové číslo: | edsair.doi.dedup.....c25b7ddcfcf438d06f36bb48d8092f91 |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | AimsMyocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown. We aimed at establishing a relevant role of cardiac inflammation in the impairment of mitochondrial energy production in advanced ischaemic and non‐ischaemic HF.MethodsWe included 81 patients with stage D HF (ICM, n = 44; DCM, n = 37) undergoing left ventricular assist device implantation (n = 59) or heart transplantation (n = 22) and obtained left ventricular tissue samples during open heart surgery. We quantified mitochondrial oxidative capacity, citrate synthase activity (CSA) and fibrosis and lymphocytic infiltration. We considered infiltration of >14 CD3+ cells/mm2 relevant inflammation.ResultsPatients with ICM or DCM did not differ regarding age (61.5 ± 5.7 vs. 56.5 ± 12.7 years, P = 0.164), sex (86% vs. 84% male, P = 0.725), type 2 diabetes mellitus (34% vs. 18%, P = 0.126) or chronic kidney disease (8% vs. 11%, P = 0.994). ICM exhibited oxidative capacity reduced by 23% compared to DCM (108.6 ± 41.4 vs. 141.9 ± 59.9 pmol/(s*mg), P = 0.006). Maximum production of reactive oxygen species was not significantly different between ICM and DCM (0.59 ± 0.28 vs. 0.69 ± 0.36 pmol/(s*ml), P = 0.196). Mitochondrial content, detected by CSA, was lower in ICM (359.6 ± 164.1 vs. 503.0 ± 198.5 nmol/min/mg protein, P = 0.002). Notably, relevant inflammation was more common in ICM (27% vs. 6%, P = 0.024), and the absolute number of infiltrating leucocytes correlated with lower oxidative capacity (r = −0.296, P = 0.019). Fibrosis was more prevalent in ICM (20.9 ± 21.2 vs. 7.2 ± 5.6% of area, P = 0.002), but not associated with oxidative capacity (r = −0.13, P = 0.327).ConclusionsMore than every fourth ICM patient with advanced HF displays myocardial inflammation in the range of inflammatory cardiomyopathy associated with reduced mitochondrial oxidative capacity. Future studies may evaluate inflammation in ICM at earlier stages in standardised fashion to explore the therapeutic potential of immunosuppression to influence trajectories of HF in ICM. |
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| ISSN: | 20555822 |
| DOI: | 10.1002/ehf2.15133 |