Effects of Tetrandrine on Growth Factor-induced DNA Synthesis and Proliferative Response of Rat Pulmonary Artery Smooth Muscle Cells

2000 ◽  
Vol 13 (2) ◽  
pp. 53-60 ◽  
Author(s):  
H.L. Wang ◽  
S.A. Kilfeather ◽  
G.R. Martin ◽  
C.P. Page
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Proliferative Response ◽  
Muscle Cells ◽  
Pulmonary Artery Smooth Muscle

Regulation of serotonin-induced DNA synthesis of bovine pulmonary artery smooth muscle cells

1994 ◽  
Vol 266 (1) ◽  
pp. L53-L60 ◽  
Author(s):  
S. L. Lee ◽  
W. W. Wang ◽  
J. J. Lanzillo ◽  
B. L. Fanburg
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Thymidine Incorporation ◽  
Muscle Cells ◽  
Dependent Manner ◽  
Actin Mrna ◽  
Pulmonary Artery Smooth Muscle ◽  
Cellular Dna

We have previously reported that serotonin [5-hydroxytryptamine (5-HT)] stimulates DNA synthesis of bovine pulmonary artery smooth muscle cells (SMC) by its high-affinity uptake. Uptake inhibitors, but not selective 5-HT receptor antagonists, prevented the stimulatory effect (S.-L. Lee and B. L. Fanburg. J. Cell. Physiol. 150:396–405, 1992). We have now further evaluated the mechanism by which 5-HT enhances SMC DNA synthesis. Although some serotonergic agonists mimicked this stimulation, selective 5-HT receptor agonists produced no or only minor and variable stimulatory effects. The action of 5-HT was not inhibited by inhibitors of phospholipases C and A2, the protein kinase C (PKC) inhibitors dihydrosphingosine and 1-(-isoquinolinylsulfonyl)-2 methylpiperazine (H-7), or down-regulation of PKC with phorbol 12,13-dibutyrate. Staurosporine, a reputed PKC and tyrosine kinase (TK) inhibitor, and genistein, a selective TK inhibitor, reversed the stimulatory effect of 5-HT in a dose-dependent manner. Before stimulation of thymidine incorporation into cellular DNA, 5-HT elevated c-myc and actin mRNAs. Imipramine, fluoxetine, staurosporine, and cholera toxin inhibited the stimulations of both DNA synthesis and c-myc and actin mRNA expressions by 5-HT. Thus the data support a concept that 5-HT-induced thymidine incorporation by SMC involves membrane transport of 5-HT that initiates tyrosine phosphorylation.

Serotonin produces both hyperplasia and hypertrophy of bovine pulmonary artery smooth muscle cells in culture

1994 ◽  
Vol 266 (1) ◽  
pp. L46-L52 ◽  
Author(s):  
S. L. Lee ◽  
W. W. Wang ◽  
J. J. Lanzillo ◽  
B. L. Fanburg
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Cellular Proliferation ◽  
Muscle Cells ◽  
Cell Surface Receptor ◽  
Quiescent State ◽  
Gene Expressions ◽  
Pulmonary Artery Smooth Muscle

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)

Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells

2002 ◽  
Vol 282 (5) ◽  
pp. L897-L903 ◽  
Author(s):  
Timothy P. Quinn ◽  
Marielle Schlueter ◽  
Scott J. Soifer ◽  
Jorge A. Gutierrez
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Vascular Development ◽  
Muscle Cells ◽  
Mechanical Stretch ◽  
Cyclic Stretch ◽  
Dependent Manner ◽  
Pulmonary Artery Smooth Muscle

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.

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