Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis

0477808 - FGÚ 2018 RIV US eng J - Journal Article
Melenovský, V. - Petrák, J. - Mráček, Tomáš - Beneš, J. - Borlaug, B. A. - Nůsková, Hana - Pluháček, T. - Špatenka, J. - Kovalčíková, Jana - Drahota, Zdeněk - Kautzner, J. - Pirk, J. - Houštěk, Josef
Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis.
European Journal of Heart Failure. Roč. 19, č. 4 (2017), s. 522-530. ISSN 1388-9842. E-ISSN 1879-0844
R&D Projects: GA ČR(CZ) GB14-36804G; GA MZd(CZ) NT14050; GA MŠMT(CZ) LQ1604; GA MZd NT14250; GA MŠMT(CZ) ED1.1.00/02.0109; GA MZd(CZ) NV16-27496A
Institutional support: RVO:67985823
Keywords : heart failure * mitochondria * iron deficiency * bioenergetics * metabolism * reactive oxygen species
OECD category: Biochemistry and molecular biology
Impact factor: 10.683, year: 2017

Iron replacement improves clinical status in iron-deficient patients with heart failure (HF), but the pathophysiology is poorly understood. The impact of myocardial iron deficiency (MID) on mitochondrial function, measured directly in the failing human heart, is unknown. Left ventricular samples were obtained from 91 consecutive HF patients and 38 HF-free organ donors (controls). Total myocardial iron content, mitochondrial respiration, citric acid cycle and respiratory chain enzyme activities, and content of OXPHOS complexes and ROS-protective enzymes were measured in tissue homogenates to quantify mitochondrial function. Myocardial iron content was lower in HF compared with controls (156 +/- 41 vs. 200 +/- 38 mu g.g(-1) dry weight, P < 0.001), independently of anaemia. MID was associated with more extensive coronary disease and less beta-blocker usage compared with non-MID HF patients. Compared with controls, HF patients displayed reduced myocardial oxygen respiration and reduced activity of all examined mitochondrial enzymes (all P < 0.001). MID in HF was associated with preserved activity of respiratory chain enzymes but reduced activity of aconitase and citrate synthase (by -26% and -15%, P < 0.05) and reduced expression of catalase, glutathione peroxidase, and superoxide dismutase 2. Myocardial iron content is decreased and mitochondrial functions are impaired in advanced HF. MID in HF is associated with diminished citric acid cycle enzyme activities and decreased ROS-protecting enzymes. MID may contribute to altered myocardial substrate use and to worsening of mitochondrial dysfunction that exists in HF.
Permanent Link: http://hdl.handle.net/11104/0278854