Mitochondria-Targeted Antioxidants: A Step towards Disease Treatment

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/; 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/; intravenous injection	(1) Reduced infarct size and troponin release; (2) Ineffectiveness on hemodynamics in the heart, or heart rate; (3) Alleviated infarction and myocardial fibrosis	[126]
SkQ1	Lifelong treatment of mice	1 or 30 nmol/	(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/; 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.