Inhibition of miR-29b in IPAH-PASMC completely recovered K<sup>+</sup> channel function and K<sub>V</sub>1.5 expression, while miR-138 and miR-222 had a partial or no effect.
Inhibition of miR-29b in IPAH-PASMC completely recovered K<sup>+</sup> channel function and K<sub>V</sub>1.5 expression, while miR-138 and miR-222 had a partial or no effect.
Additionally, overexpression of miR-29b in normal PASMC decreased large-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> (BK<sub>Ca</sub>) channel currents and downregulated BK<sub>Ca</sub> channel β1 subunit (BK<sub>Ca</sub>β1 or KCNMB1) expression, while inhibition of miR-29b in IPAH-PASMC increased BK<sub>Ca</sub> channel activity and BK<sub>Ca</sub>β1 levels.
Inhibition of miR-29b in IPAH-PASMC completely recovered K<sup>+</sup> channel function and K<sub>V</sub>1.5 expression, while miR-138 and miR-222 had a partial or no effect.
In this study, we examined the expression of FGL2 in idiopathic pulmonary arterial hypertension (IPAH) patients, and in monocrotaline-induced rat and hypoxia-induced mouse PH models.
Here, we demonstrate the increased levels of LRP1 protein in the lungs of idiopathic pulmonary arterial hypertension (IPAH) patients, hypoxia-exposed mice, and monocrotaline-treated rats.
Furthermore, LRP1 silencing attenuated the expression of fibronectin and collagen I and increased the levels of α-smooth muscle actin and myocardin in donor, but not in IPAH, PASMC.
Taken together, using weighted gene coexpression analysis, YWHAB was identified and validated in association with IPAH progression, which might serve as a biomarker and/or therapeutic target for IPAH.
Comparative transcriptomic analysis and functional assays revealed an intrinsic role for PAXIP1-AS1 in orchestrating the hyperproliferative and migratory actions of IPAH smooth muscle cells.
In addition, specificity protein 1 (SP1), a known stimulator of VEGF expression, was shown to have higher O-GlcNAc levels in IPAH compared to control at physiological (5 mM) and high (25 mM) glucose concentrations, and knockdown resulted in decreased VEGF protein levels.
LOX was found to be increased in serum of SSc patients and was suggested to be related to skin fibrosis, yet a vascular source of LOX has been demonstrated in idiopathic pulmonary arterial hypertension (iPAH).
Furthermore, p53 is downregulated in PASMCs isolated from patients with idiopathic pulmonary arterial hypertension compared with PASMCs from normal subjects.
We investigated the ADAMTS13-von Willebrand factor (VWF) axis in CTEPH, including its relationship with disease severity, inflammation, <i>ABO</i> groups and <i>ADAMTS13</i> genetic variants.ADAMTS13 and VWF plasma antigen levels were measured in patients with CTEPH (n=208), chronic thromboembolic disease without pulmonary hypertension (CTED) (n=35), resolved pulmonary embolism (n=28), idiopathic pulmonary arterial hypertension (n=30) and healthy controls (n=68).
Thus we provide evidence that suggests FGL2 prothrombinase presents a potential therapeutic target for clinical treatment of PH.<b>NEW & NOTEWORTHY</b> This is the first study to demonstrate that fibrinogen-like protein 2 (FGL2) participates in the pathological progression of pulmonary hypertension (PH) in human idiopathic pulmonary arterial hypertension, a monocrotaline rat PH model, and a hypoxia mouse PH model.
The gene encoding human bone morphogenetic protein 9 (<i>BMP9</i>) was identified as a novel genetic locus displaying exome-wide association with IPAH in the discovery cohort (OR 18.8; p=1.9×10<sup>-11</sup>).