Pulmonary artery smooth muscle cells

Holland et al. [125] have shown that the potent vascular smooth muscle cell mitogen and phospholipase A2 activator thrombin stimulated superoxide production in human endothelial cells, which was inhibited by the NADPH oxidase inhibitors. Similarly, thrombin enhanced the production of oxygen species and the expression of )Alphos and Rac2 subunits of NADPH oxidase in VSMCs [126,127]. Greene et al. [128] demonstrated that the activator of NO synthase neuropeptide bradykinin is also able to stimulate NADPH oxidase in VSMCs. Similar to XO, NADPH oxidase enhanced superoxide production in pulmonary artery smooth muscle cells upon exposure to hypoxia [129]. 

James PF, Grupp IL, Grupp G et al 1999 Identification of a specific role for the Na,K-ATPase a2 isoform as a regulator of calcium in the heart. Mol Cell 3 555—563 Janiak R, Wilson, SM, Montague S, Hume JR 2001 Heterogeneity of calcium stores and elementary release events in canine pulmonary arterial smooth muscle cells. Am J Physiol 280 C22-C33... 

Serotonin (5-HT) produces a rapid elevation of superoxide that stimulates the mitogenesis of bovine pulmonary artery smooth muscle cells (SMCs). EGb scavenges superoxide elevated by 5-HT, hence preventing 5-HT-induced mitogenesis on both SMCs and Chinese hamster lung fibroblasts. These results indicate that EGb inhibits the cellular transduction signaling process that leads to mitogenesis, as a result of its antioxidant activity [141]. 

Figure 12.9 Endothelial cell-specific nuclear import of plasmids. Growth-arrested African Green Monkey kidney epithelial cells (TC7), human pulmonary artery smooth muscle cells (HSMCs) and human umbilical vein endothelial cells (HUYECs) were microinjected in the nucleus (top) and cytoplasm with CMV-driven, GFP-expressing plasmids containing either no additional sequences (open bars), the SV40 enhancer (striped bars), or the flk-1 promoter (shaded bars). Eight hours after injection, the cells were visualized for GFP expression by fluorescence microscopy. Whereas all three plasmids supported GFP expression when delivered into the nucleus of all three cell types, only the SV40 enhancer mediated nuclear import and gene expression in all cells when injected into the cytoplasm. As predicted, the flk-1 promoter caused import and expression only in cells in which transcription factors necessary for its expression and import were made, namely endothelial cells.

Monkey kidney epithelial cells (TC7), human pulmonary artery smooth muscle cells... 

Sweeney, M., Yu, Y., Platoshyn, O., Zhang, S., McDaniel, S. S. and Yuan, J. X., 2002, Inhibition of endogenous TRP1 decreases capacitative Ca2+ entry and attenuates pulmonary artery smooth muscle cell proliferation. Am J Physiol Lung Cell Mol Physiol 283, L144—55. 

Weir, E., Wyatt, CN, Reeve, HL, Huang, J, Archer, SL, and Peers, C (1994). Diphenyleneiodonium inhibits both potassium and calcium currents in isolated pulmonary artery smooth muscle cells. J Appl Physiol 76(6) 2611-2615. 

The pathophysiology of PAH is thought to be due to unchecked cellular proliferation of the vascular wall, obliteration of the small and medium sized vessels, and in situ thrombosis with loss of the capillaries and small vessels. Endothelial dysfunction and vascular damage is accompanied by an imbalance of the proliferative vasoconstrictors (endothelin, thromboxane, serotonin) versus growth inhibitor vasodilators (prostacyclin, nitric oxide) with an increase in the pulmonary artery smooth muscle cells (PASMC) [Ca2+] and the loss of the apop-totic response to unchecked growth. 

Nakayama, D. K., Geller, D. A., Di Silvio, M., Blooragarden, G., Davies, P., Pitt, B., Hatakey-ama, K., Kagamiyama, H., Simmons, R. L., and Billiar, T. R. (1994). Increased activity of de novo tetrahydrobiopterin synthesis in pulmonary artery smooth muscle cells stimulated to produce nitric oxide. Am. J. Physiol. 266, L455-L460. 

Garg HG, Hales CA, Yu L, Butler M, Islam T, Xie J, Linhardt RJ. Increase in the growth inhibition of bovine pulmonary artery smooth muscle cells by an O-hexanoyl low-molecular-weight heparin derivative. Carbohydr Res 2006 341 2607-2612. 

Wedgwood S, Dettman RW, Black SM ET-1 stimulates pulmonary arterial smooth muscle cell proliferation via induction of reactive oxygen species. Am J Physiol Lung Cell Mol Physiol 2001 28LL1058-L1067. 

Go-6976, a Ca -dependent protein kinase isozyme inhibitor, reduced responses to angiotensin II however, it did not alter responses to serotonin, norepinephrine, or U-46619, whereas Go-6976 enhanced BAY K 8644 responses (De Witt et al. 2001). Rottle-rin, a protein kinase C-6 isozyme/calmodulin-dependent kinase III inhibitor, reduced responses to angiotensin II and norepinephrine, did not alter responses to serotonin or U-46619, and enhanced responses to BAY K 8644. Immunohistochemistry of feline pulmonary arterial smooth muscle cells demonstrated localisation of protein kinase C-a and -6 isozymes in response to 12-0-tetradecano-phorbol-13-acetate and angiotensin II. Localisation of protein kinase C-a and -8 isozymes decreased with administration of Go-6976 and rottlerin, respectively. 

Exposure of foetal sheep pulmonary artery smooth muscle cells to endothelin-1 resulted in increases in superoxide production and viable foetal pulmonary artery smooth muscle cells after 72 h (Wedgwood et al. 2001). These increases were prevented by pre-treatment with the ETa receptor agonist PD-156707 (1 /iM). Treatment with pertussis toxin blocked the effects of endothelin-1. Wortman-nin, LY-294002, diphenyleneiodonium, 4-(2-amino-ethyl)benzenesulphonyl fluoride, and apocynin also prevented the endothelin-1-mediated increases in superoxide production and viable cell numbers. Exposure to H2O2 or diethyldithiocarbamate increased viable cell number by 37 % and 50 %, respectively. 

Chronic hypoxia causes pulmonary arterial smooth muscle cell depolarisation, elevated endothelin-1, and vasoconstriction. Resting [Ca li in smooth muscle cells from intrapulmonary arteries of rats exposed to 10 % O2 for 21 days was 293.9 25.2 nM (vs. 153.6 28.7nM in normoxia) (Shimoda et al. 2000). Resting [Ca " ] was decreased after extracellular Ca removed but not with nifedipine (10" M), an L-type Ca " channel antagonist. After chronic hypoxia, the endothelin-1-induced increase in [Ca ]i was reduced and was aboHshed after extracellular Ca removal or nifedipine. Removal of extracellular Ca " reduced endothehn-1-induced tension however, nifedipine had only a slight effect. 

Second, oleanolic acid (43) could induce their early phosphorylation of two such as p38 mitogen-activated protein kinase (p38 MAPK) of) a class of mitogen-activated protein kinases that are responsive to the stress stimuli such as cytokines, ultraviolet irradiation, heat shock, osmotic shock, cell differentiation, apoptosis and autophagy and p42/44 mitogen-activated protein kinase (p42/44 MAPK) [31] that regulated by p53 mitogen-activated protein kinase and nitric oxide in human pulmonary arterial smooth muscle cells. However, oleanolic acid (43) could not induce the early phosphorylation of c-Jun N-terminal kinase-1 (JNK-1) [32] that mediate both survival and apoptosis of tumor cells [33]. 

Mizuno S, Kadowaki M, Demura Y, Ameshima S, Miyamori 1, Ishizaki T. p42/44 Mitogen-activated protein kinase regulated by p53 and nitric oxide in human pulmonary arterial smooth muscle cells. Am J Respir Cell Mol Biol 3l 2), 184-192,2004. 

Lee S, Park M, So I, Earm Y. NADH and NAD modulates Ca +-activated K" " channels in small pulmonary arterial smooth muscle cells of the rabbit. Pflugers Arch 1994 427 378-380. 

Gurney AM, Osipenko ON, MacMillan D, Kempsill FEJ. Potassiirm charmels rmderlying the testing membrane potential of pulmonary artery smooth muscle cells. Clin Exp Pharmacol Physiol 2002 29(4) 330-333. 

In vitro (pulmonary arterial smooth muscle cells) transfection mediated You et al. (2015)... 

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