Over the last few decades, there has been a huge improvement in the treatment of cardiovascular diseases. The development of early coronary artery reperfusion therapies has dramatically reduced the morbidity and mortality associated with acute myocardial infarction. In addition, there has been a great advance in the understanding of the importance of cardiovascular prevention, with significant enhancement of preventive strategies targeting high blood pressure, metabolic syndrome and high cholesterol levels. Unfortunately, the fight against cardiovascular diseases has not yet been won, and myocardial infarction, stroke and heart failure still represent the most common cause of death worldwide. It is, therefore, of crucial importance to develop new therapies to treat these diseases and to identify new therapeutic targets.
However, this difficult task is possible only if the molecular mechanisms underlying the development and progression of myocardial injury and vascular damage in response to stress are fully clarified. Mitochondrial dysfunction has now emerged as an important mechanism underlying the development of cardiovascular diseases. Studies have demonstrated that mitochondrial complex disruption, mitochondrial uncoupling and structural abnormalities, such as cristae remodeling and swelling, are observed during myocardial ischemia or chronic cardiac remodeling and heart failure. These are, in part, secondary to mitochondrial complex disruption and mPTP opening. As a consequence of mitochondrial damage, reactive oxygen species accumulate, ATP production dramatically decreases and cell death occurs. In order to limit mitochondrial damage, particularly during stress, cells activate important mechanisms to ensure mitochondrial quality control and turnover. In particular, mitochondrial dynamics and autophagy are of paramount importance for the maintenance of mitochondrial function and structure. Mitochondria continuously fuse and divide, depending on conditions in the cell, and several proteins regulate this fusion and fission. Specifically, Opa1 and mitofusins 1/2 promote fusion, whereas Drp1 and Fis1 induce fission. Healthy mitochondria may fuse with impaired ones in order to functionally repair the damage. In addition, mitochondria may fuse to boost their oxidative capacity.
On the other hand, in the presence of irreversible damage, mitochondrial fission allows the removal of the altered portions, which are then degraded by autophagy. Autophagy is an intracellular degradation process that removes damaged proteins and organelles via vesicles called autophagosomes, which then fuse with lysosomes to degrade the sequestered cargos. Mitophagy is a type of autophagy that selectively removes damaged mitochondria and represents one of the most important mechanisms of mitochondrial turnover. When mitochondria are damaged, the E3-ubiquitin ligase, Parkin, is recruited by the kinase, PINK1. Once recruited, Parkin ubiquitinates proteins of the outer mitochondrial membrane, allowing autophagosomes to recognize and sequester the damaged mitochondria. However, recent evidence suggests that mitophagy can also be Parkin-independent. Although the basic understanding of mitochondrial dynamics and mitophagy is continuously increasing, these two processes still warrant clarification, particularly in the cardiovascular system. The mechanisms of regulation and the functions of fusion, fission and mitophagy in the heart in response to ischemia/reperfusion injury, chronic remodeling, mechanical stress, genetic cardiomyopathies, metabolic disorders and chemotherapy toxicity still need to be fully dissected. In addition, the relevance of mitochondrial dynamics and autophagy in the vasculature, particularly in the development of endothelial dysfunction and atherosclerosis, is also unclear.
For these reasons, this Research Topic is open to scientific contributions addressing the role of mitochondrial dysfunction in cardiovascular diseases, with a particular focus on mitochondrial quality control mechanisms. Both basic and translational studies are welcome, and the editors welcome submission of all types of papers on this topic, including original articles, short communications and reviews.
Over the last few decades, there has been a huge improvement in the treatment of cardiovascular diseases. The development of early coronary artery reperfusion therapies has dramatically reduced the morbidity and mortality associated with acute myocardial infarction. In addition, there has been a great advance in the understanding of the importance of cardiovascular prevention, with significant enhancement of preventive strategies targeting high blood pressure, metabolic syndrome and high cholesterol levels. Unfortunately, the fight against cardiovascular diseases has not yet been won, and myocardial infarction, stroke and heart failure still represent the most common cause of death worldwide. It is, therefore, of crucial importance to develop new therapies to treat these diseases and to identify new therapeutic targets.
However, this difficult task is possible only if the molecular mechanisms underlying the development and progression of myocardial injury and vascular damage in response to stress are fully clarified. Mitochondrial dysfunction has now emerged as an important mechanism underlying the development of cardiovascular diseases. Studies have demonstrated that mitochondrial complex disruption, mitochondrial uncoupling and structural abnormalities, such as cristae remodeling and swelling, are observed during myocardial ischemia or chronic cardiac remodeling and heart failure. These are, in part, secondary to mitochondrial complex disruption and mPTP opening. As a consequence of mitochondrial damage, reactive oxygen species accumulate, ATP production dramatically decreases and cell death occurs. In order to limit mitochondrial damage, particularly during stress, cells activate important mechanisms to ensure mitochondrial quality control and turnover. In particular, mitochondrial dynamics and autophagy are of paramount importance for the maintenance of mitochondrial function and structure. Mitochondria continuously fuse and divide, depending on conditions in the cell, and several proteins regulate this fusion and fission. Specifically, Opa1 and mitofusins 1/2 promote fusion, whereas Drp1 and Fis1 induce fission. Healthy mitochondria may fuse with impaired ones in order to functionally repair the damage. In addition, mitochondria may fuse to boost their oxidative capacity.
On the other hand, in the presence of irreversible damage, mitochondrial fission allows the removal of the altered portions, which are then degraded by autophagy. Autophagy is an intracellular degradation process that removes damaged proteins and organelles via vesicles called autophagosomes, which then fuse with lysosomes to degrade the sequestered cargos. Mitophagy is a type of autophagy that selectively removes damaged mitochondria and represents one of the most important mechanisms of mitochondrial turnover. When mitochondria are damaged, the E3-ubiquitin ligase, Parkin, is recruited by the kinase, PINK1. Once recruited, Parkin ubiquitinates proteins of the outer mitochondrial membrane, allowing autophagosomes to recognize and sequester the damaged mitochondria. However, recent evidence suggests that mitophagy can also be Parkin-independent. Although the basic understanding of mitochondrial dynamics and mitophagy is continuously increasing, these two processes still warrant clarification, particularly in the cardiovascular system. The mechanisms of regulation and the functions of fusion, fission and mitophagy in the heart in response to ischemia/reperfusion injury, chronic remodeling, mechanical stress, genetic cardiomyopathies, metabolic disorders and chemotherapy toxicity still need to be fully dissected. In addition, the relevance of mitochondrial dynamics and autophagy in the vasculature, particularly in the development of endothelial dysfunction and atherosclerosis, is also unclear.
For these reasons, this Research Topic is open to scientific contributions addressing the role of mitochondrial dysfunction in cardiovascular diseases, with a particular focus on mitochondrial quality control mechanisms. Both basic and translational studies are welcome, and the editors welcome submission of all types of papers on this topic, including original articles, short communications and reviews.
