Activation of the renin-angiotensin system (RAS) contributes to vascular remodeling observed in many diseases, including idiopathic pulmonary arterial hypertension.
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.
After adjustment for clinical features, a BMPR2 mutation and haemodynamics, a lower NOx level remained an increased risk of mortality.Patients with IPAH had lower levels of plasma NOx, which correlated inversely with mPAP, PVR and survival.
Alpha-1-antitrypsin and vitronectin were down-regulated in IPAH and may be valuable candidates for further explorations of their roles in the development of IPAH.
Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins.
Among these, the finding of an association between PPH and the L-allelic variant of the serotonin transporter (5-HTT) gene indicates that 5-HTT, which controls smooth muscle hyperplasia, probably contributes to susceptibility to PPH or is an important modifier of the PPH phenotype.
Blockade of TRPM7 by 2-APB or TRPV4 by Ruthenium red inhibited shear stress-induced rise in [Ca(2+)]cyt in normal and IPAH-PASMC, while activation of TRPM7 by bradykinin or TRPV4 by 4αPDD induced greater increase in [Ca(2+)]cyt in IPAH-PASMC than in normal PASMC.
Capsaicin induced phosphorylation of CREB by raising [Ca<sup>2+</sup>]<sub>cyt</sub>, and capsaicin-induced CREB phosphorylation were significantly enhanced in IPAH PASMCs compared with normal PASMCs.
Comparable upregulation was confirmed (1) after full establishment of hypoxia-induced PH, (2) in 2 rat models of PH (monocrotaline-treated and hypoxic rats treated with the vascular endothelial growth factor receptor antagonist SU5416), and (3) in lungs from patients with idiopathic pulmonary arterial hypertension.
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.
Compared with control subjects, we found the following in patients with IPAH: elevated CCL2 protein levels in plasma and lung tissue, whereas monocyte CCL2 levels were similar between patients and control subjects, and elevated CCL2 release by P-ECs or PA-SMCs.
Compared with controls, protein expression of HIF-1α and Twist-related protein-1 (TWIST1) was decreased ( P < 0.05), and miRNA-543 and ET-1 expression increased ( P < 0.001) in hPASMCs from patients with IPAH.
Compared with controls, protein expression of HIF-1α and Twist-related protein-1 (TWIST1) was decreased ( P < 0.05), and miRNA-543 and ET-1 expression increased ( P < 0.001) in hPASMCs from patients with IPAH.
Compared with healthy MACs, IPAH MACs exhibited (1) significantly lower levels of endothelial markers as shown by fluorescence microscopy; (2) a markedly higher rate of apoptosis under both normal culture condition and serum starvation as shown by the TUNEL assay; (3) significantly decreased migration towards vascular endothelial growth factor as shown by a modified Boyden chamber migration assay; and (4) similar vascular endothelial growth factor and endothelial nitric oxide synthase mRNA levels as shown by reverse transcription quantitative PCR.