Targeting Mitochondrial Dynamics Proteins for the Development of Therapies for Cardiovascular Diseases
Abstract
:1. Introduction
2. The Role of Mitochondria in Cardiac Functioning
2.1. ATP Production
2.2. Calcium Homeostasis
2.3. Lipid Synthesis
3. Processes of Mitochondrial Dynamics in the Heart Muscle
3.1. Mitochondrial Fusion
3.2. Mitochondrial Fission
3.3. Mitophagy
3.4. Mitochondrial Biogenesis
4. Mitochondrial Dynamics Disorders in Cardiovascular Diseases
4.1. Mitophagy Disorders
4.2. Mitochondrial Transport Disorders
4.3. Mitochondrial Biogenesis Disorders
4.4. Mitochondrial Fission Disorders
4.5. Mitochondrial Fusion Disorders
5. Analysis of Mitochondrial Dynamics Proteins as Therapeutic Targets
5.1. Impact on Mitophagy Proteins
5.2. Impact on Mitochondrial Fission Proteins
5.3. Impact on Mitochondrial Fusion Proteins
6. Discussions
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Disease | Model | Disruption of Mitochondrial Dynamics |
---|---|---|
Atherosclerosis | Mice, human cardiomyocyte culture | Decreased mitophagy |
Heart failure | Mice, human cardiomyocyte culture | Decreased mitophagy |
Ischemic heart disease | Mice | Increased mitophagy at the beginning of the IRI and decreased at the end of the IRI |
Heart failure | Mice | Decreased mitochondrial transport |
Mitochondrial cardiomyopathy | Human cardiomyocyte culture | Increased mitochondrial biogenesis |
Hypertrophic cardiomyopathy | Human cardiomyocyte culture | Decreased mitochondrial biogenesis |
Heart failure | Mice | Increased mitochondrial fission and decreased fusion |
Metabolic cardiomyopathy | Rats | Increased mitochondrial fission and decreased fusion |
Therapy Compound | Action Mechanism | Study Type | Results |
---|---|---|---|
Liraglutide | Mitophagy strengthening through SIRT1 expression increasing | Animal model | Restoring myocardial function after a heart attack |
Melatonin (1) | Activation of mitophagy | Animal models | Improving clinical symptoms of atherosclerosis and diabetic cardiomyopathy |
Berberine | Activation of mitophagy | Animal model | Restoration of cardiac function in heart failure |
mitoTEMPOL | Inhibition of mitophagy | Animal model | |
mdivi-1 | Suppression of the GTPase activity of DRP1 | Animal model | Protection from ischemia/reperfusion and reduction in the possibility of myocardial infarction |
P110 peptides | Inhibition of the DRP1 binding with Fis1 | Animal model and cell model | Protection from septic cardiomyopathy development |
Exenatide | Inhibition of the mitochondrial localization of Drp1 | Cell model and clinical trial | Heart regeneration in cell model but no significant improvement in cardiac function in clinical trial |
Resveratrol | Inhibition of the Drp1expression | Animal models and clinical trial | Improvement of clinical symptoms from patients with coronary heart disease |
HO1 | Increase in Mfn1/2 expression | Animal model | |
Melatonin (2) | Increase in Mfn2 expression | Animal model | Attenuation of post-infarction injury |
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Blagov, A.V.; Kozlov, S.; Blokhina, T.; Sukhorukov, V.N.; Orekhov, A.N. Targeting Mitochondrial Dynamics Proteins for the Development of Therapies for Cardiovascular Diseases. Int. J. Mol. Sci. 2022, 23, 14741. https://doi.org/10.3390/ijms232314741
Blagov AV, Kozlov S, Blokhina T, Sukhorukov VN, Orekhov AN. Targeting Mitochondrial Dynamics Proteins for the Development of Therapies for Cardiovascular Diseases. International Journal of Molecular Sciences. 2022; 23(23):14741. https://doi.org/10.3390/ijms232314741
Chicago/Turabian StyleBlagov, Alexander V., Sergey Kozlov, Tatiana Blokhina, Vasily N. Sukhorukov, and Alexander N. Orekhov. 2022. "Targeting Mitochondrial Dynamics Proteins for the Development of Therapies for Cardiovascular Diseases" International Journal of Molecular Sciences 23, no. 23: 14741. https://doi.org/10.3390/ijms232314741