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

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

doi:https://dx.doi.org/10.1002/ejhf.640

Number of the records: 1

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

1.

SYSNO ASEP	0477808
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis
Author(s)	Melenovský, V. (CZ) Petrák, J. (CZ) Mráček, Tomáš (FGU-C)_{RID, ORCID} Beneš, J. (CZ) Borlaug, B. A. (US) Nůsková, Hana (FGU-C)_{RID, ORCID} Pluháček, T. (CZ) Špatenka, J. (CZ) Kovalčíková, Jana (FGU-C) Drahota, Zdeněk (FGU-C)_{RID, ORCID} Kautzner, J. (CZ) Pirk, J. (CZ) Houštěk, Josef (FGU-C)_{RID, ORCID}
Source Title	European Journal of Heart Failure - ISSN 1388-9842 Roč. 19, č. 4 (2017), s. 522-530
Number of pages	9 s.
Language	eng - English
Country	US - United States
Keywords	heart failure ; mitochondria ; iron deficiency ; bioenergetics ; metabolism ; reactive oxygen species
Subject RIV	EB - Genetics ; Molecular Biology
OECD category	Biochemistry and molecular biology
R&D Projects	GB14-36804G GA ČR - Czech Science Foundation (CSF)
	NT14050 GA MZd - Ministry of Health (MZ)
	LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	NT14250 GA MZd - Ministry of Health (MZ)
	ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	NV16-27496A GA MZd - Ministry of Health (MZ)
Institutional support	FGU-C - RVO:67985823
UT WOS	000401004500011
EID SCOPUS	84988378043
DOI	https://doi.org/10.1002/ejhf.640
Annotation	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.
Workplace	Institute of Physiology
Contact	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Year of Publishing	2018

Number of the records: 1