Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms
| Autor: | Toon A.B. van Veen, Chantal J. M. van Opbergen, Lyanne den Braven, Mario Delmar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Heart disease Physiology Cardiomyopathy Disease Review 030204 cardiovascular system & hematology Mitochondrion Bioinformatics medicine.disease_cause lcsh:Physiology Sudden cardiac death connexin 43 Pathogenesis 03 medical and health sciences cardiac metabolism 0302 clinical medicine Fibrosis Physiology (medical) Medicine oxidative stress lcsh:QP1-981 business.industry arrhythmogenic cardiomyopathy medicine.disease ATP mitochondria 030104 developmental biology calcium handling business plakophillin-2 Oxidative stress |
| Zdroj: | Frontiers in Physiology, 10. Frontiers Research Foundation Frontiers in Physiology Frontiers in Physiology, Vol 10 (2019) |
| ISSN: | 1664-042X |
| DOI: | 10.3389/fphys.2019.01496 |
| Popis: | Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease, associated with ventricular arrhythmias, fibrofatty replacement of the myocardial mass and an increased risk of sudden cardiac death (SCD). Malignant ventricular arrhythmias and SCD largely occur in the pre-clinical phase of the disease, before overt structural changes occur. To prevent or interfere with ACM disease progression, more insight in mechanisms related to electrical instability are needed. Currently, numerous studies are focused on the link between cardiac arrhythmias and metabolic disease. In line with that, a potential role of mitochondrial dysfunction in ACM pathology is unclear and mitochondrial biology in the ACM heart remains understudied. In this review, we explore mitochondrial dysfunction in relation to arrhythmogenesis, and postulate a link to typical hallmarks of ACM. Mitochondrial dysfunction depletes adenosine triphosphate (ATP) production and increases levels of reactive oxygen species in the heart. Both metabolic changes affect cardiac ion channel gating, electrical conduction, intracellular calcium handling, and fibrosis formation; all well-known aspects of ACM pathophysiology. ATP-mediated structural remodeling, apoptosis, and mitochondria-related alterations have already been shown in models of PKP2 dysfunction. Yet, the limited amount of experimental evidence in ACM models makes it difficult to determine whether mitochondrial dysfunction indeed precedes and/or accompanies ACM pathogenesis. Nevertheless, current experimental ACM models can be very useful in unraveling ACM-related mitochondrial biology and in testing potential therapeutic interventions. |
| Databáze: | OpenAIRE |
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