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. 2019 Aug 13;20(16):3938. doi: 10.3390/ijms20163938

Table 3.

Studies dealing with pulmonary hypertension (EC: endothelial cells; HPASMCs: human pulmonary arterial smooth muscle cells; MCT-PAH: monocrotaline pulmonary artery hypertension; PAH: pulmonary artery hypertension; SMC: smooth muscle cells).

Pulmonary Hypertension
Humans
Study Disease Sample miRNAs Findings
Potus et al. (2014) [77] Pulmonary hypertension Humans: percutaneous biopsy of vastus lateralis (n = 11 patients, n = 9 controls).
Animals: male Sprague-Dawley rats.
Cells: CD311 cells isolated from two idiopathic PAH, two heritable PAH, and three control quadriceps biopsies		 miR-126 AntagomiR-126 in healthy CD31+ cells mimicked the PAH phenotype. In skeletal muscle of healthy rats, it decreased muscle capillarity (p < 0.05) and exercise tolerance in treadmill tests (p < 0.05)
Animals
Study Disease Sample miRNAs Findings
Pullamsetti et al. (2012) [25] Pulmonary hypertension Animals: mice and rat models.
Cells: pooled human umbilical vein ECs and human pulmonary artery SMCs		 miR-17, miR-21, miR-92a Ant-17 and Ant-21 reduced right ventricular systolic pressure, all antagomirs decreased pulmonary arterial muscularization. Ant-17 reduced hypoxia-induced right ventricular hypertrophy, improved pulmonary artery acceleration time. In rats, Ant-17 decreased right ventricular systolic pressure and total pulmonary vascular resistance index, increased pulmonary artery acceleration time, normalized cardiac output, and decreased pulmonary vascular remodeling. In human pulmonary artery smooth muscle cells, Ant-17 increased p21
Brock et al. (2014) [39] Pulmonary hypertension Animals: four mice samples (three in hypoxic condition, one control).
In vitro: HPASMCs		 miR-20a Animals: AntagomiR-20a enhanced BMPR2 expression levels in lung tissues by 59.3% (p < 0.001), reduced wall thickness (p < 0.01), luminal occlusion of small pulmonary arteries (p < 0.001) and right ventricular hypertrophy (p < 0.01).
In vitro: Transfection of HPASMCs with antimiR-20a activates downstream targets of BMPR2 increasing activation of Id-1 and Id-2 (p < 0.05). HPASMCs proliferation reduced upon transfection with antagomiR-20a (p < 0.05)
Potus et al. (2014) [77] Pulmonary hypertension Humans: percutaneous biopsy of vastus lateralis (n = 11 patients, n = 9 controls).
Animals: male Sprague-Dawley rats.
Cells: CD311 cells isolated from two idiopathic PAH, two heritable PAH, and three control quadriceps biopsies		 miR-126 AntagomiR-126 in healthy CD31+ cells mimicked the PAH phenotype. In skeletal muscle of healthy rats, it decreased muscle capillarity (p < 0.05) and exercise tolerance in treadmill tests (p < 0.05)
Sharma et al. (2015) [57] Pulmonary hypertension Male Sprague-Dawley rats miR-206 Knockdown of miR-206 reduced right ventricular pressure and right ventricular hypertrophy index
Gubrij et al. (2016) [78] Pulmonary hypertension MCT-PAH rats miR-223 A223 reduced levels of miR-223 in pulmonary artery and lungs of MCT PAH rats as compared to controls (p < 0.05), but did not attenuate MCT PAH (p > 0.05)
Mondejar-Parreño et al. (2019) [51] Pulmonary hypertension Pathogen-free male Wistar rats miR-1 AntagomiR-1 prevented (p < 0.05) hypoxia-induced decline in voltage-dependent potassium channel Kv1.5 currents
Cell Lines
Study Disease Sample miRNAs Findings
Pullamsetti et al. (2012) [25] Pulmonary hypertension Animals: mice and rat models.
Cells: pooled human umbilical vein ECs and human pulmonary artery SMCs		 miR-17, miR-21, miR-92a Ant-17 and Ant-21 reduced right ventricular systolic pressure, all antagomirs decreased pulmonary arterial muscularization. Ant-17 reduced hypoxia-induced right ventricular hypertrophy, improved pulmonary artery acceleration time. In rats, Ant-17 decreased right ventricular systolic pressure and total pulmonary vascular resistance index, increased pulmonary artery acceleration time, normalized cardiac output, and decreased pulmonary vascular remodeling. In human pulmonary artery smooth muscle cells, Ant-17 increased p21
Brock et al. (2014) [39] Pulmonary hypertension Animals: four mice samples (three in hypoxic condition, one control).
In vitro: HPASMCs		 miR-20a Animals: AntagomiR-20a enhanced BMPR2 expression levels in lung tissues by 59.3% (p < 0.001), reduced wall thickness (p < 0.01), luminal occlusion of small pulmonary arteries (p < 0.001) and right ventricular hypertrophy (p < 0.01).
In vitro: Transfection of HPASMCs with antimiR-20a activates downstream targets of BMPR2 increasing activation of Id-1 and Id-2 (p < 0.05). HPASMCs proliferation reduced upon transfection with antagomiR-20a (p < 0.05)
Potus et al. (2014) [77] Pulmonary hypertension Humans: percutaneous biopsy of vastus lateralis (n = 11 patients, n = 9 controls).
Animals: male Sprague-Dawley rats.
Cells: CD311 cells isolated from two idiopathic PAH, two heritable PAH, and three control quadriceps biopsies		 miR-126 AntagomiR-126 in healthy CD31+ cells mimicked the PAH phenotype. In skeletal muscle of healthy rats, it decreased muscle capillarity (p < 0.05) and exercise tolerance in treadmill tests (p < 0.05)