Hypercapnia downregulates hypoxia‐induced lysyl oxidase expression in pulmonary artery smooth muscle cells via inhibiting transforming growth factor β1signalling

2019 ◽  
Vol 37 (3) ◽  
pp. 193-202 ◽  
Author(s):  
Xiao‐dong Xia ◽  
Yan‐ping Peng ◽  
Dan Lei ◽  
Wei‐qian Chen
2020 ◽  
Vol 98 (9) ◽  
pp. 629-636 ◽  
Author(s):  
Hidekazu Maruyama ◽  
Satoshi Sakai ◽  
Laurence Dewachter ◽  
Céline Dewachter ◽  
Benoit Rondelet ◽  
...  

The increase in thickening of the arterial wall of pulmonary arterial hypertension (PAH) includes cellular proliferation as well as matrix deposition and interrupted internal elastic lamina (IEL) consisting of a thick homogeneous sheet of elastin. Little is, although, known about the detail of IEL formation in PAH. Endothelin-1 is overexpressed in pulmonary arterioles of PAH. We aimed to examine the expression of genes contributing to IEL formation in pulmonary artery smooth muscle cells (PASMCs) especially focused on lysyl oxidase (LOx), an exreacellular matrix enzyme that catalyzes the cross-linking of collagens or elastin. We quantified mRNA expressions of genes contributing to IEL formation including LOx in PASMCs using real-time quantitative polymerase chain reaction. We stimulated human PASMCs with endothelin-1 with prostacyclin or trapidil. Endothelin-1 significantly increased LOx expression. Prostacyclin and trapidil restored endothelin-1-induced LOx expression to the basal level. Endothelin-1 increased LOx expression strongly in PASMCs from PAH patients compared to those from controls. Trapidil reduced LOx expression only in PASMCs from PAH patients. Overexpressed endothelin-1 in PAH patients can increase expression of LOx and agitate cross-linking of elastin and collagen, resulting in ectopic deposition of these in the vascular media.


1994 ◽  
Vol 266 (1) ◽  
pp. L46-L52 ◽  
Author(s):  
S. L. Lee ◽  
W. W. Wang ◽  
J. J. Lanzillo ◽  
B. L. Fanburg

Serotonin [5-hydroxytryptamine (5-HT)] has a dual effect on bovine pulmonary artery smooth muscle cells (SMC) in culture (S.-L. Lee, W. W. Wang, B. J. Moore, and B. L. Fanburg. Circ. Res. 68: 1362–1368, 1991.). Cellular internalization of 5-HT stimulates DNA synthesis and cellular proliferation, whereas the action of 5-HT on a cell surface receptor elevates adenosine 3',5'-cyclic monophosphate and inhibits proliferation. The present study shows that 5-HT causes proliferation of both pulmonary artery and aortic SMC but not of endothelial cells or fibroblasts. Furthermore, c-myc and alpha- and beta-actin gene expressions of pulmonary artery SMC were elevated after 2-h incubation with 5-HT, before stimulation of [3H]thymidine incorporation. Actinomycin D (0.05 micrograms/ml) but not cycloheximide (1 microgram/ml) inhibited the gene expression produced by 5-HT. Growth-arrested SMC progressed from a G0 quiescent state through a normal cell cycle when subjected to 5-HT, 5-HT plus 25 ng/ml insulin-like growth factor, or 5-HT plus 0.5 ng/ml fibroblast growth factor. Cell number increased by 20–40% at 40 h and 50–140% at 7 days. Protein content of cells treated with 5-HT was elevated by 20–40% at 7 days, whereas the rate of protein synthesis, measured by [35S]methionine incorporation, increased by 50–70% at 24 h. In the presence of 1 microM 5-HT, cells enlarged by 70 and 100–200% at 40 h and 7 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


2002 ◽  
Vol 282 (5) ◽  
pp. L897-L903 ◽  
Author(s):  
Timothy P. Quinn ◽  
Marielle Schlueter ◽  
Scott J. Soifer ◽  
Jorge A. Gutierrez

Vascular endothelial growth factor (VEGF) and basic (b) fibroblast growth factor (FGF-2/bFGF) are involved in vascular development and angiogenesis. Pulmonary artery smooth muscle cells express VEGF and FGF-2 and are subjected to mechanical forces during pulsatile blood flow. The effect of stretch on growth factor expression in these cells is not well characterized. We investigated the effect of cyclic stretch on the expression of VEGF and FGF-2 in ovine pulmonary artery smooth muscle cells. Primary confluent cells from 6-wk-old lambs were cultured on flexible silicon membranes and subjected to cyclic biaxial stretch (1 Hz; 5–25% stretch; 4–48 h). Nonstretched cells served as controls. Expression of VEGF and FGF-2 was determined by Northern blot analysis. Cyclic stretch induced expression of both VEGF and FGF-2 mRNA in a time- and amplitude-dependent manner. Maximum expression was found at 24 h and 15% stretch (VEGF: 1.8-fold; FGF-2: 1.9-fold). These results demonstrate that mechanical stretch regulates VEGF and FGF-2 gene expression, which could play a role in pulmonary vascular development or in postnatal pulmonary artery function or disease.


1997 ◽  
Vol 25 (3) ◽  
pp. 446-452 ◽  
Author(s):  
Charles J. Shanley ◽  
Mehrnaz Gharaee-Kermani ◽  
Rajabrata Sarkar ◽  
Theodore H. Welling ◽  
Andrew Kriegel ◽  
...  

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