AimsGenetic hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere protein-encoding genes (i.e. genotype-positive HCM). In an increasing number of patients, HCM occurs in the absence of a mutation (i.e. genotype-negative HCM). Mitochondrial dysfunction is thought to be a key driver of pathological remodelling in HCM. Reports of mitochondrial respiratory function and specific disease-modifying treatment options in patients with HCM are scarce.Methods and resultsRespirometry was performed on septal myectomy tissue from patients with HCM (n = 59) to evaluate oxidative phosphorylation and fatty acid oxidation. Mitochondrial dysfunction was most notably reflected by impaired NADH-linked respiration. In genotype-negative patients, but not genotype-positive patients, NADH-linked respiration was markedly depressed in patients with an indexed septal thickness ≥10 compared with <10. Mitochondrial dysfunction was not explained by reduced abundance or fragmentation of mitochondria, as evaluated by transmission electron microscopy. Rather, improper organization of mitochondria relative to myofibrils (expressed as a percentage of disorganized mitochondria) was strongly associated with mitochondrial dysfunction. Pre-incubation with the cardiolipin-stabilizing drug elamipretide and raising mitochondrial NAD+ levels both boosted NADH-linked respiration.ConclusionMitochondrial dysfunction is explained by cardiomyocyte architecture disruption and is linked to septal hypertrophy in genotype-negative HCM. Despite severe myocardial remodelling mitochondria were responsive to treatments aimed at restoring respiratory function, eliciting the mitochondria as a drug target to prevent and ameliorate cardiac disease in HCM. Mitochondria-targeting therapy may particularly benefit genotype-negative patients with HCM, given the tight link between mitochondrial impairment and septal thickening in this subpopulation.
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We collected, reviewed and edited articles submitted to Sustainability on the topic of communicative and behavioral interventions to increase sustainability.In this Special Issue, we would like to highlight research on interventions. How we can find interventions that help in encouraging (sustainable or less consumption) the use of fossil-free methods of transport, the implementation of renewable energy, etc. We invite you to submit your work to this Special Issue on “Communicative and Behavioral Interventions to Increase Sustainability” that contribute to the establishment of a sustainable future. We would like to collect a Special Issue that highlight evidence-based interventions to change behavior to establish the sustainable society.This Special Issue is positioned to bring together the best work on communicative and behavioral interventions. It can include (but is not limited to) dialogue, stakeholder engagement, educational programs, nudging, community building, corporate social responsibility (CSR), social innovations, etc. We would like you to focus on evidence-based interventions and encourage practical insights or ideas for applications of findings
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