The Therapeutic Strategies Targeting Mitochondrial Metabolism in Cardiovascular Disease
Abstract
:1. Introduction
2. Mitochondrial Metabolism Dysfunction in CVD
3. Major Factors in Mitochondrial Metabolism
3.1. Mitochondrial DNA
3.2. Mitochondrial Dynamics
3.2.1. Mitochondrial Fusion
3.2.2. Mitochondrial Fission
3.3. Mitochondrial Calcium
3.3.1. Mitochondrial Calcium Transport
3.3.2. [Ca2+]m and Mitochondrial Metabolism
3.4. ROS
4. Mitochondrial Metabolism Disorder and CVD
4.1. PAH
4.2. Aortic Aneurysm
4.3. Atherosclerosis
4.4. Heart Failure
5. Mitochondria-Targeted Therapeutic Agents and Strategies in CVD
5.1. Potential Mitochondrial Targets for CVD
5.1.1. MPTP
5.1.2. Sirtuin 3 (Sirt3)
5.1.3. [Ca2+]m
5.1.4. Mitochondrial Dynamics
5.2. Mitochondria-Targeted Agents for CVD
5.2.1. CoQ10 and MitoQ
5.2.2. Melatonin
5.2.3. SS-31
5.2.4. MitoTEMPOL
5.2.5. MitoSNO
5.3. Mitochondria-Targeted Gene Therapy Strategies
5.3.1. Mitochondria-Targeted Gene Editing Technologies
5.3.2. Ectopic Expression of Mitochondrial Proteins
5.3.3. Mitochondrial Replacement Therapy (MRT) Technologies
6. Prospection
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Disease | Animals Model | Results and/or Possible Mechanism | Reference |
---|---|---|---|
Heart diseases | Doxorubicin induced cardiotoxicity in rats | Melatonin exerts cardioprotective efficacy by preserving mitochondrial function and dynamics | [183,184] |
Cardiac I/R injury in prediabetic obese rats | Melatonin exerts cardioprotective effects against cardiac I/R injury in prediabetic obese rats by activation of modulating melatonin receptor 2 | [185] | |
Myocardial I/R injury in a DCD heart rat model | Melatonin exerts cardioprotective effects by activation of the JAK2/STAT3 signaling pathway | [186] | |
MI rat model induced by ligation of the left anterior descending coronary artery | Melatonin exerts cardioprotective effects by promoting cardiomyocyte proliferation and heart regeneration, and by inhibiting pyroptosis and cardiac fibrosis | [187,188,189] | |
A murine cardiac hypertrophy model by transverse aortic constriction | Melatonin ameliorates pressure overload-induced cardiac hypertrophy by attenuating Atg5-dependent autophagy and activating the Akt/mTOR pathway | [190] | |
Isoprenaline hydrochloride induced acute heart failure in aged rat | Melatonin prevents the mitochondrial dysfunction by increasing the CNPase level | [191] | |
Atherosclerosis | High-fat diet treated ApoE knockout mice | Melatonin decreases pro-inflammatory macrophage polarization, vulnerable plaque rupture, endothelial cell injury and atherosclerotic plaque | [192,193,194,195,196] |
Aneurysm | Rat AAA model | Melatonin prevents AAA formation through anti-inflammatory, antioxidative and anti-autophagy effects | [179,197] |
TAAD mouse model | Melatonin exerts therapeutic effects against TAAD by reducing oxidative stress and SMC loss via activation of Sirt1 signaling | [178] | |
PAH | Hypoxia-induced PAH in mice | Melatonin inhibits inflammasome-associated activation of endothelium and macrophages in PAH | [181] |
Dasatinib aggravated rat experimental model of hypoxic PAH | Melatonin attenuates dasatinib-induced PAH by inhibiting oxidative damage and apoptosis of ECs and inhibiting abnormal proliferation of SMCs | [198] | |
MCT-induced rat PAH model | Melatonin treatment reduces MCT-induced RV hypertrophy, fibrosis, and remodeling | [199] | |
A chronically hypoxia-induced PAH of the newborn sheep model | Melatonin improves vasodilatory function by enhancing the vasodilator prostanoid pathway | [200] |
Disease | Study Title | Melatonin Dose | Outcome | Clinical Trials.gov Identifier |
---|---|---|---|---|
Heart failure | Effect of melatonin on cardiovascular and muscle mass and function in patients with heart failure | 10 mg tablets orally every night for 24 weeks | Unknown | NCT03894683 |
Coronary artery disease | Melatonin impact on the outcomes of myocardial I/R injury during coronary artery bypass grafting surgery | 60 mg/day 5 days before surgery | Ongoing | NCT05552586 |
Coronary artery disease | Enhanced recovery after surgery in coronary artery bypass graft/off-pump coronary artery bypass | 5 mg in the evening | Unknown | NCT03956420 |
Coronary artery disease | Melatonin on coronary artery calcification | 3 mg/day for 6 months | Unknown | NCT03966235 |
Acute coronary syndrome | Effects of melatonin on reperfusion injury | Intravenous 11.61 mg | Unknown | NCT03303378 |
Essential hypertension | Melatonin and essential arterial hypertension | 1 mg/day for 1 year | Ongoing | NCT05257291 |
Hypertension | Trial of oral melatonin in elevated blood pressure | 3 mg for three weeks | Ongoing | NCT03764020 |
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Huang, X.; Zeng, Z.; Li, S.; Xie, Y.; Tong, X. The Therapeutic Strategies Targeting Mitochondrial Metabolism in Cardiovascular Disease. Pharmaceutics 2022, 14, 2760. https://doi.org/10.3390/pharmaceutics14122760
Huang X, Zeng Z, Li S, Xie Y, Tong X. The Therapeutic Strategies Targeting Mitochondrial Metabolism in Cardiovascular Disease. Pharmaceutics. 2022; 14(12):2760. https://doi.org/10.3390/pharmaceutics14122760
Chicago/Turabian StyleHuang, Xiaoyang, Zhenhua Zeng, Siqi Li, Yufei Xie, and Xiaoyong Tong. 2022. "The Therapeutic Strategies Targeting Mitochondrial Metabolism in Cardiovascular Disease" Pharmaceutics 14, no. 12: 2760. https://doi.org/10.3390/pharmaceutics14122760