title: Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis.
abstract: Iron replacement improves clinical status in iron-deficient patients with heart failure (HF), but the pathophysiology is poorly understood. Iron is essential not only for erythropoiesis, but also for cellular bioenergetics. 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 undergoing transplantation and 38 HF-free organ donors (controls). Total myocardial iron content, mitochondrial respiration, citric acid cycle and respiratory chain enzyme activities, respiratory chain components (complex I-V), and protein content of reactive oxygen species (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 µg·g-1dry weight, P < 0.001), independently of anaemia. MID (the lowest iron tercile in HF) 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 oxygen2respiration 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.
authors.affiliation: Department of Cardiology and Cardiac Surgery, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Melenovsky
authors.affiliation: Department of Pathological Physiology and BIOCEV, First Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Petrak
authors.affiliation: Department of Bioenergetics, Institute of Physiology, Academy of Sciences, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Mracek
authors.affiliation: Department of Cardiology and Cardiac Surgery, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Benes
authors.affiliation: Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
authors.forename: Barry A
authors.initials: BA
authors.lastname: Borlaug
authors.affiliation: Department of Bioenergetics, Institute of Physiology, Academy of Sciences, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Nuskova
authors.affiliation: Department of Analytical Chemistry and RCPTM, Faculty of Science, Palacky University, Olomouc, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Pluhacek
authors.affiliation: Department of Transplantation and Tissue Bank, University Hospital in Motol, Prague, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Spatenka
authors.affiliation: Department of Bioenergetics, Institute of Physiology, Academy of Sciences, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Kovalcikova
authors.affiliation: Department of Bioenergetics, Institute of Physiology, Academy of Sciences, Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Drahota
authors.affiliation: Department of Cardiology and Cardiac Surgery, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Kautzner
authors.affiliation: Department of Cardiology and Cardiac Surgery, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Pirk
authors.affiliation: Department of Bioenergetics, Institute of Physiology, Academy of Sciences, Prague, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Houstek
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*
chemical_list: D007501:Iron
keywords: Bioenergetics; Heart failure; Iron deficiency; Metabolism; Mitochondria; Reactive oxygen species