Table 2.

Promising compounds targeting hypoxia and the mitochondrial ROS and ER stress signaling pathways in animal models of pulmonary hypertension and preeclampsia.

Compound	Mode of action	Animal model	Pulmonary hypertension			Preeclampsia			Reference
			Pulmonary artery pressure (PAP)/right ventricular systolic pressure (RVSP)	Right ventricle hypertrophy	Pulmonary artery remodeling	Mean arterial pressure	Proteinuria	Fetal growth
Hypoxia inducible factor (HIF) pathway
2-methoxyestradiol	HIF-1α inhibition	Hypoxic rats	↓	↓	↓				[239]
2-methoxyestradiol	HIF-1α inhibition	COMT−/− mice				↓	↓		[254]
Apigenin	HIF-1α inhibition	Hypoxic rats	↓	↓	↓				[240]
Baicalin	HIF-1α inhibition	Hypoxic rats	↓	↓	↓				[241]
C76	HIF-2α inhibition	Egln1Tie2Cre mice, monocrotaline (MCT) rats, Sugen/hypoxic rats	↓	↓	↓				[242]
Caffeic acid phenethyl ester	HIF-1α inhibition	MCT rats	↓	↓	↓				[251]
Celastramycin	HIF-1α inhibition	Hypoxic mice, MCT rats, Sugen/hypoxic rats	↓	↓	↓				[243]
Cyclosporin A	HIF-1α inhibition	Hypoxic rats	↓	↓	↓				[244]
Digoxin	HIF-1α inhibition	Hypoxic mice	↓	↓	↓				[245]
Emetine	HIF-1α and HIF-2α inhibition	MCT rats, Sugen/hypoxic rats	↓	↓	↓				[246]
Melatonin	HIF-1α inhibition	Hypoxic rats	↓	↓	↓				[247]
PT2567	HIF-2α inhibition	Hypoxic rats		↓	↓				[248]
Topotecan	HIF-1α inhibition	Hypoxic rats	↓	↓	↓				[249]
YC-1	HIF-1α inhibition	Hypoxic mice	↓	↓	↓				[250]
R59949	PHD2 activation	Hypoxic mice	↓	↓	↓				[252]
Anti-CD146 antibody	HIF-1α inhibition	Hypoxic mice	↓	↓	↓				[253]
HIF-1α small hairpin RNA (shRNA)	HIF-1α silencing	Hypoxic rats	↓		↓				[112]
Anti-miR-210 oligonucleotide	microRNA-210 (miR-210) inhibition	Sugen/hypoxic mice	↓		↓				[149]
mitoROS
Melatonin	mitoROS scavenger	RUPP rats				↓			[257]
MitoQ	Mitochondria-targeted antioxidant	Hypoxic mice	↔	↓	↔				[259]
MitoQ	Mitochondria-targeted antioxidant	RUPP rats				↓		↑	[263]
MitoQ	Mitochondria-targeted antioxidant	RUPP mice				↓		↑	[197]
MitoQ	Mitochondria-targeted antioxidant	Hypoxic sheep						↑	[262]
MitoQ-nanoparticles (NPs)	Mitochondria-targeted antioxidant	Hypoxic rats						↑	[260, 261]
Mito-Tempo	Mitochondria-targeted antioxidant	RUPP rats				↓		↑	[263]
ER stress and the unfolded protein response (UPR)
4-PBA	ER stress inhibition	Hypoxic mice MCT rats	↓	↓	↓	↓			[101]
4-PBA	ER stress inhibition	Hypoxic mice	↓	↓	↓	↓			[102]
4-PBA	ER stress inhibition	MCT rats	↓	↓	↓	↓			[217, 266]
GSK2606414	PERK inhibition	Sugen/hypoxic rats	↓	↓	↓	↓			[267]
H2S	ER stress inhibition	Hypoxic rats	↓	↓	↓				[268]

Abbreviations: 4-PBA, 4-phenylbutyric acid; C76, compound 76; COMT, catechol-O-methyltransferase; H2S, hydrogen sulfide; MitoQ, Mitochondrial-targeted coenzyme Q; RUPP, reduced uterine perfusion pressure; YC-1, 3-(5’-hydroxymethyl-2’-furyl)-1-benzylindazole.