Mitochondrial Dysfunction and Heart Disease: Critical Appraisal of an Overlooked Association.
Giandomenico BisacciaFabrizio RicciSabina GallinaAngela Di BaldassarreBarbara GhinassiPublished in: International journal of molecular sciences (2021)
The myocardium is among the most energy-consuming tissues in the body, burning from 6 to 30 kg of ATP per day within the mitochondria, the so-called powerhouse of the cardiomyocyte. Although mitochondrial genetic disorders account for a small portion of cardiomyopathies, mitochondrial dysfunction is commonly involved in a broad spectrum of heart diseases, and it has been implicated in the development of heart failure via maladaptive circuits producing and perpetuating mitochondrial stress and energy starvation. In this bench-to-bedside review, we aimed to (i) describe the key functions of the mitochondria within the myocardium, including their role in ischemia/reperfusion injury and intracellular calcium homeostasis; (ii) examine the contribution of mitochondrial dysfunction to multiple cardiac disease phenotypes and their transition to heart failure; and (iii) discuss the rationale and current evidence for targeting mitochondrial function for the treatment of heart failure, including via sodium-glucose cotransporter 2 inhibitors.
Keyphrases
- heart failure
- oxidative stress
- left ventricular
- ischemia reperfusion injury
- acute heart failure
- reactive oxygen species
- atrial fibrillation
- cardiac resynchronization therapy
- cell death
- clinical trial
- genome wide
- pulmonary hypertension
- endoplasmic reticulum
- dna methylation
- drug delivery
- angiotensin ii
- copy number
- combination therapy
- stress induced