Mitochondrial Therapies in Heart Failure.
The current therapy for patients with stable systolic heart failure is largely limited to treatments that interfere with neurohormonal activation. Critical pathophysiological hallmarks of heart failure are an energetic deficit and oxidative stress, and both may be the result of mitochondrial dysfunction. This dysfunction is not (only) the result of defect within mitochondria per se, but is in particular traced to defects in intermediary metabolism and of the regulatory interplay between excitation-contraction coupling and mitochondrial energetics, where defects of cytosolic calcium and sodium handling in failing hearts may play important roles. In the past years, several therapies targeting mitochondria have emerged with promising results in preclinical models. Here, we discuss the mechanisms and results of these mitochondria-targeted therapies, but also of interventions that were not primarily thought to target mitochondria but may have important impact on mitochondrial biology as well, such as iron and exercise. Future research should be directed at further delineating the details of mitochondrial dysfunction in patients with heart failure to further optimize these treatments.
Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, 66421, Homburg, Germany.
Albrecht
A
von Hardenberg
Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, 66421, Homburg, Germany. Christoph.maack@uks.eu.
Christoph
C
Maack
D000975:Antioxidants / Q000627:therapeutic use*; D019587:Dietary Supplements; D005081:Exercise Therapy; D006333:Heart Failure / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007501:Iron / Q000627:therapeutic use; D008929:Mitochondria, Heart / Q000378:metabolism*; D009842:Oligopeptides / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D014131:Trace Elements / Q000627:therapeutic use*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use*
D000975:Antioxidants; D009842:Oligopeptides; D009943:Organophosphorus Compounds; D014131:Trace Elements; D014815:Vitamins; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; D014451:Ubiquinone; C429014:mitoquinone; D007501:Iron; C024989:coenzyme Q10
Calcium; Energetics; Heart failure; Mitochondria; Reactive oxygen species