Mechanical, cellular, and molecular factors interact to modulate circulating endothelial cell progenitors

2004 ◽  
Vol 286 (5) ◽  
pp. H1985-H1993 ◽  
Author(s):  
Chunlin Wang ◽  
Chunhua Jiao ◽  
Heather D. Hanlon ◽  
Wei Zheng ◽  
Robert J. Tomanek ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Transforming Growth Factor ◽  
Vascular Endothelial Cell ◽  
Muscle Cells ◽  
Cyclic Stretch ◽  
Cardiovascular Cells ◽  
The Impact

It appears that there are two classes of human circulating endothelial cell (EC) progenitors, CD34+and CD34–CD14+cells. Attention has focused on CD34+cells, yet CD34–CD14+monocytic cells are far more abundant and may represent the most common class of circulating EC progenitor. Little is known about molecular or physiological factors that regulate putative CD34–CD14+EC progenitor function, although factors secreted by other blood and cardiovascular cells to which they are exposed probably affect their behavior. Hypoxia and stretch are two important physiological stimuli known to trigger growth factors in cardiovascular cells and accordingly may modulate EC progenitors. To investigate the impact of these environmental parameters on EC progenitors, EC production in CD34–CD14+cultures was evaluated. Our data indicate that neither stretch nor hypoxia alters EC production by EC progenitors directly but do so indirectly through their effects on cardiovascular cells. Conditioned media (CM) from coronary artery smooth muscle cells inhibit EC production in culture, and this inhibition is stronger if the coronary smooth muscle cells have been subjected to cyclic stretch. In contrast, cardiomyocyte CM increases EC cell number, an effect that is potentiated if the myocytes have been subjected to hypoxia. Significantly, EC progenitor responses to CM are altered by the presence of CD34–CD14–peripheral blood mononuclear cells (PBMCs). Moreover, CD34–CD14–PBMCs attenuate EC progenitor responsiveness to the angiogenic factors basic fibroblast growth factor (FGF-2), vascular endothelial cell growth factor-A165, and erythropoietin while inducing EC progenitor death in the presence of transforming growth factor-β1in vitro

scholarly journals TGF-β suppresses the upregulation of MMP-2 by vascular smooth muscle cells in response to PDGF-BB

2010 ◽  
Vol 298 (1) ◽  
pp. C191-C201 ◽  
Author(s):  
George M. Risinger ◽  
Dawn L. Updike ◽  
Elizabeth C. Bullen ◽  
James J. Tomasek ◽  
Eric W. Howard
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Transforming Growth Factor ◽  
Focal Adhesions ◽  
Muscle Cells ◽  
Threshold Level ◽  
Inhibitory Signaling

During platelet-derived growth factor (PDGF)-BB-mediated recruitment to neovascular sprouts, vascular smooth muscle cells (VSMCs) dedifferentiate from a contractile to a migratory phenotype. This involves the downregulation of contractile markers such as smooth muscle (SM) α-actin and the upregulation of promigration genes such as matrix metalloproteinase (MMP)-2. The regulation of MMP-2 in response to PDGF-BB is complex and involves both stimulatory and inhibitory signaling pathways, resulting in a significant delay in upregulation. Here, we provide evidence that the delay in MMP-2 upregulation may be due to the autocrine expression and activation of transforming growth factor (TGF)-β, which is known to promote the contractile phenotype in VSMCs. Whereas PDGF-BB could induce the loss of stress fibers and focal adhesions, TGF-β was able to block or reverse this transition to a noncontractile state. TGF-β did not, however, suppress early signaling events stimulated by PDGF-BB. Over time, though PDGF-BB induced increased TGF-β1 levels, it suppressed TGF-β2 and TGF-β3 expression, leading to a net decrease in the total TGF-β pool, resulting in the upregulation of MMP-2. Together, these findings indicate that MMP-2 expression is suppressed by a threshold level of active TGF-β, which in turn promotes a contractile VSMC phenotype that prevents the upregulation of MMP-2.

EGF and TGF-beta regulate neutral endopeptidase expression in renal vascular smooth muscle cells

1997 ◽  
Vol 272 (6) ◽  
pp. C1836-C1843 ◽  
Author(s):  
P. L. Tharaux ◽  
A. Stefanski ◽  
S. Ledoux ◽  
J. M. Soleilhac ◽  
R. Ardaillou ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Transforming Growth Factor ◽  
Muscle Cells ◽  
Neutral Endopeptidase ◽  
Tgf Beta ◽  
Renal Vascular

We recently reported that neutral endopeptidase (NEP) expression on renal vascular smooth muscle cells (VSMC) was downregulated in the presence of serum. Here we examine the role of epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGF-beta) in this downregulation and the consequences of the changes in NEP activity on their mitogenic effects. EGF inhibited NEP activity, whereas TGF-beta was stimulatory. Expression of the enzyme was studied by measuring the binding of [125I]RB-104, a specific NEP inhibitor, and the fluorescence intensity of NEP-labeled cells. Both parameters were decreased by EGF and were increased by TGF-beta. NEP mRNA expression in EGF-treated cells was reduced after 48 h. In contrast, it was increased in TGF-beta-treated cells. Interestingly, NEP inhibition influenced the mitogenic effect of EGF. Indeed, thiorphan, an NEP inhibitor, and an anti-NEP antibody decreased EGF-dependent [3H]thymidine incorporation and cell proliferation by approximately 50%. TGF-beta had no effect on VSMC growth. These results indicate that EGF but not TGF-beta participates in the downregulatory potency of serum on NEP expression in VSMC. They also demonstrate that the full effect of EGF on VSMC proliferation depends on intact NEP activity.

Cyclic stretch activates p38 SAPK2-, ErbB2-, and AT1-dependent signaling in bladder smooth muscle cells

2000 ◽  
Vol 279 (4) ◽  
pp. C1155-C1167 ◽  
Author(s):  
Hiep T. Nguyen ◽  
Rosalyn M. Adam ◽  
Samuel H. Bride ◽  
John M. Park ◽  
Craig A. Peters ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Mapk Pathway ◽  
Muscle Cells ◽  
Cyclic Stretch ◽  
Bladder Smooth Muscle ◽  
Erk Mapk

Cyclic mechanical stretch of bladder smooth muscle cells (SMC) increases rates of DNA synthesis and stimulates transcription of the gene for heparin-binding epidermal growth factor-like growth factor (HB-EGF), an ErbB1/EGF receptor ligand that has been linked to hypertrophic bladder growth. In this study we sought to clarify the signaling pathways responsible for mechanotransduction of the stretch stimulus. HB-EGF mRNA levels, DNA synthesis, and AP-1/Ets DNA binding activities were induced by repetitive stretch of primary culture rat bladder SMC. Inhibitors of the p38 SAPK2 pathway, the angiotensin receptor type 1 (AT1), and the ErbB2 tyrosine kinase reduced each of these activities, while an inhibitor of the extracellular signal-regulated kinase mitogen-activated protein kinase (Erk-MAPK) pathway had no effect. Stretch rapidly activated stress-activated protein kinase 2 (p38 SAPK2) and Jun NH2-terminal kinase (JNK)/SAPK pathways but not the Erk-MAPK pathway and induced ErbB2 but not ErbB1 phosphorylation. Angiotensin II (ANG II) a bladder SMC mitogen previously linked to the stretch response, did not activate ErbB2, and ErbB2 activation occurred in response to stretch in the presence of an ANG receptor inhibitor, indicating that activation of the AT1-mediated pathway and the ErbB2-dependent pathway occurs by independent mechanisms. p38 SAPK2 and JNK/SAPK signaling also appeared to be independent of the ErbB2 and AT1 pathways. These findings indicate that stretch-stimulated DNA synthesis and gene expression in normal bladder SMC occur via multiple independent receptor systems (e.g., AT1 and ErbB2) and at least one MAPK pathway (p38 SAPK2). Further, we show that the Erk-MAPK pathway, which in most systems is linked to receptor-dependent cell growth responses, is not involved in progression to DNA synthesis or in the response of the HB-EGF gene to mechanical forces.

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