Table 4.
MTAs in cardiovascular disease (CVD) models.
| Mitochondria-targeted antioxidants/bioactive component | Models/clinical trials | Dosage | Effects/mechanism | Reference |
|---|---|---|---|---|
| Mito-TEMPO | THP-1 cell model induced by ox-LDL; high-fat dietary-fed rats | 20 μmol/L; 0.7 mg/kg∗bodyweight; intraperitoneal administration | (1) Attenuated foam cell formation via promoting autophagic flux (2) Increased cholesterol efflux via autophagy-dependent ABCA1 and ABCG1 upregulation (3) Reversed the accumulation of TC and LDL-c |
[125] |
|
| ||||
| MitoSNO | Open chest mouse model | 100 ng/kg∗bodyweight; intravenous injection | (1) Reduced infarct size and troponin release (2) Ineffectiveness on hemodynamics in the heart, dP/dtmax or heart rate (3) Alleviated infarction and myocardial fibrosis |
[126] |
|
| ||||
| SkQ1 | Lifelong treatment of mice | 1 or 30 nmol/kg∗bodyweight | (1) Prevented spontaneous cardiomyopathy (2) Decreased age-related heart hypertrophy and diffuse fibrosis (3) Affected cell adhesion-related gene expressions, one of which had mitochondrial localization |
[127] |
|
| ||||
| MitoQ | Pressure overload-induced heart failure in rats | 100 μmol/L in drinking water | (1) Reduced ventricular hypertrophy and lung congestion (2) Restored membrane potential in IFM (3) Improved retention capacity of mitochondrial calcium in the SSM and IFM |
[128] |
| Pressure overload-induced cardiac fibrosis in rats | 2 μmol; oral gavage | (1) Attenuated apoptosis, hypertrophic remodeling, fibrosis, and left ventricular dysfunction (2) Blunted TGF-β1 and NOX4 upregulation (3) Prevented Nrf2 downregulation and rescued TGF-β1 activation (4) Ameliorated the cardiac remodeling dysregulation in phenylephrine and TGF-β1-induced models |
[129] | |
| Rat model of prenatal hypoxia | 125 μmol; intravenous injection | (1) Improved vasorelaxation (2) Alleviated oxidative stress in placental cells (3) Prevented the decrease in vascular sensitivity to phenylephrine of their offspring |
[130] | |
| Mouse model of aortic stiffening | 250 μmol/L in drinking water | (1) Decreased pulse wave velocity in old mice (2) Rescued the decrease of elastin region elastic modulus and elastin expression (3) Reversed in vivo aortic stiffness |
[131] | |
|
| ||||
| MitoE | Bovine aortic endothelial cells induced by hydrogen peroxide and glucose oxidase | 1 μmol/L in culture medium | (1) Abrogated H2O2- and lipid peroxide-induced oxidative protein (2) Inhibited cytochrome c release, caspase 3 activation, and DNA fragmentation (3) Inhibited transferrin receptor-dependent iron uptake and apoptosis |
[132] |
|
| ||||
| SS-20, SS-31 | Rat model of myocardial infarction | 3 mg/kg∗bodyweight; intraperitoneal injection | (1) Reduced lipid peroxidation (2) Decreased the occurrence frequency and severity of arrhythmia |
[133] |
|
| ||||
| SS-31/elamipretide/MTP-131 | Clinical trials on heart failure patients | 20 mg subcutaneous injection 4 and 40 mg intravenous injection |
(1) High-dose SS-31 improved left ventricular volumes (2) Improved super complex-associated oxygen flux, complex (C) I activity |
NCT02388464
[78] |
| Clinical trials on reperfusion injury patients | Intravenous at 0.05 mg/kg/h | (1) Conjunction SS-31 with standard therapy is superior to placebo for reducing myocardial infarction |
NCT01572909
[124] |
|
Notes: CF: cardiac fibroblasts; IFM: interfibrillar mitochondria; LDL-c: high-density lipoprotein cholesterol; lncRNAs: long noncoding RNAs; NOX4: NADPH oxidase subunit 4; Nrf2: nuclear factor erythroid 2; ox-LDL: oxidized high-density lipoprotein; SSM: subsarcolemmal mitochondria; TC: total cholesterol; TEMPO: 4-hydroxy-2,2,6,6-tetramethylpiperidin-N-oxide; TGF-β1: transforming growth factor β 1.