scholarly journals Glucocorticoids stimulate collagen and noncollagen protein synthesis in cultured vascular smooth muscle cells.

1984 ◽  
Vol 98 (2) ◽  
pp. 541-549 ◽  
Author(s):  
D C Leitman ◽  
S C Benson ◽  
L K Johnson
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Specific Activity ◽  
Fold Increase ◽  
Muscle Cells ◽  
Type I ◽  
Twofold Increase ◽  
In Cells

The effect of glucocorticoids on collagen synthesis was examined in cultured bovine aortic smooth muscle (BASM) cells. BASM cells treated with 0.1 microM dexamethasone during their proliferative phase (11 d) were labeled with [3H]proline for 24 h, and the acid-precipitable material was incubated with bacterial collagenase. Dexamethasone produced an approximate twofold increase in the incorporation of proline into collagenase-digestible protein (CDP) and noncollagen protein (NCP) in the cell layer and medium. The stimulation was present in both primary mass cultures and cloned BASM. An increase in CDP and NCP was detected at 0.1 nM, while maximal stimulation occurred at 0.1 microM. Only cells exposed to dexamethasone during their log phase of growth (1-6 d after plating) showed the increase in CDP and NCP when labeled 11 d after plating. The stimulatory effect was observed in BASM cells treated with the natural bovine glucocorticoid, cortisol, dexamethasone, and testosterone, but was absent in cells treated with aldosterone, corticosterone, cholesterol, 17 beta-estradiol, and progesterone. The increase in CDP and NCP was absent in cells treated with the inactive glucocorticoid, epicortisol, and totally abolished by the antagonist, 17 alpha-hydroxyprogesterone, suggesting that the response was mediated by specific cytoplasmic glucocorticoid receptors. Dexamethasone-treated BASM cells showed a 4.5-fold increase in the specific activity of intracellular proline, which was the result of a twofold increase in the uptake of proline and depletion of the total proline pool. After normalizing for specific activity, dexamethasone produced a 2.4- and 2.8-fold increase in the rate of collagen and NCP synthesis, respectively. Cells treated with dexamethasone secreted 1.7-fold more collagen protein in 24 h compared to control cultures. The BASM cells secreted 70% Type I and 30% Type III collagen into the media as assessed by two-dimensional gel electrophoresis. The ratio of these two types was not altered by dexamethasone. The results of the present study demonstrate that glucocorticoids can act directly on vascular smooth muscle cells to increase the synthesis and secretion of collagen and NCP.

scholarly journals Collagen degradation and platelet-derived growth factor stimulate the migration of vascular smooth muscle cells

2000 ◽  
Vol 113 (11) ◽  
pp. 2055-2064
Author(s):  
E. Stringa ◽  
V. Knauper ◽  
G. Murphy ◽  
J. Gavrilovic
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cell ◽  
Collagen Type ◽  
Muscle Cells ◽  
Collagen Type I ◽  
Type I

Cell migration is a key event in many biological processes and depends on signals from both extracellular matrix and soluble motogenic factors. During atherosclerotic plaque development, vascular smooth muscle cells migrate from the tunica media to the intima through a basement membrane and interstitial collagenous matrix and proliferate to form a neointima. Matrix metalloproteinases have previously been implicated in neointimal formation and in this study smooth muscle cell adhesion and migration on degraded collagen have been evaluated. Vascular smooth muscle cells adhered to native intact collagen type I and to its first degradation by-product, 3/4 fragment (generated by collagenase-3 cleavage), unwound at 35 degrees C to mimic physiological conditions. PDGF-BB pre-treatment induced a fourfold stimulation of smooth muscle cell motility on the collagen 3/4 fragment whereas no increase in smooth muscle cell motility on collagen type I was observed. Cell migration on collagen type I was mediated by alpha2 integrin, whereas PDGF-BB-stimulated migration on the 3/4 collagen fragment was dependent on alphavbeta3 integrin. alphavbeta3 integrin was organised in clusters concentrated at the leading and trailing edges of the cells and was only expressed when cells were exposed to the 3/4 collagen fragment. Tyrphostin A9, an inhibitor of PDGF receptor-beta tyrosine kinase activity, resulted in complete abolition of migration of PDGF-BB treated cells on collagen type I and 3/4 fragment. These results strongly support the hypothesis that the cellular migratory response to soluble motogens can be regulated by proteolytic modification of the extracellular matrix.

Regulation of endothelin-mediated calcium mobilization in vascular smooth muscle cells by isoproterenol

1991 ◽  
Vol 260 (3) ◽  
pp. C492-C502 ◽  
Author(s):  
Y. T. Xuan ◽  
W. D. Watkins ◽  
A. R. Whorton
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Inositol Phosphates ◽  
Fold Increase ◽  
Muscle Cells ◽  
Beta Agonist ◽  
Intracellular Camp ◽  
Permeabilized Cells

We have investigated the effect of isoproterenol on endothelin-induced Ca2+ mobilization in A10 vascular smooth muscle cells. Endothelin (ET) stimulates a rapid and sustained elevation of intracellular Ca2+ mediated by production of inositol phosphates, release of intracellular Ca2+, and activation of a plasmalemmal Ca2+ influx pathway. This influx pathway appears to be a L-type channel because it is inhibited by nicardipine and activated by BAY K 8644. Depolarization of the cells, by elevating extracellular K+, activated a pharmacologically similar channel and produced a similar change in intracellular Ca2+ concentration. Preincubation of cells with isoproterenol reduced the peak Ca2+ response to endothelin and blocked the sustained elevation. However, isoproterenol did not alter K(+)-induced Ca2+ entry. Thus it appears that ET-induced entry is mediated by intracellular signals and not by depolarization. With the use of cells incubated in Ca2(+)-free medium containing 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, isoproterenol was shown to inhibit Ca2+ release from intracellular pools by 36 +/- 3%. Furthermore, isoproterenol pretreatment or addition of adenosine 3',5'-cyclic monophosphate (cAMP) to saponin-permeabilized cells inhibited inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]-induced Ca2+ release from intracellular sites. Similar effects were seen with forskolin. Propranolol reversed the inhibitory effects of isoproterenol. Isoproterenol pretreatment also inhibited the rapid formation of Ins(1,4,5)P3 and [2-3H]inositol 1,3,4,5-tetrakisphosphate stimulated by endothelin and reduced the sustained formation of these compounds. Finally, isoproterenol and forskolin led to a greater than 10-fold increase in intracellular cAMP levels. This stimulation of adenylate cyclase by isoproterenol was completely blocked by propranolol. It appears then that the beta-agonist isoproterenol interacts with a beta-adrenergic receptor, elevates cAMP, and thereby alters endothelin-induced Ca2+ mobilization. Inhibition of Ins(1,4,5)P3 formation, reduction in the responsiveness of the Ins(1,4,5)P3 intracellular receptor, and perhaps inhibition of ET-induced Ca2+ entry appear to be involved.

Abstract 667: Angiotensin II-induced Osteopontin Expression in Vascular Smooth Muscle Cells involves G q/11 , Ras, ERK, Src and Ets-1.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Keiko Abe ◽  
Mari Ishida ◽  
Mariko Sawano ◽  
Hidekatsu Nakashima ◽  
Nwe Nwe Soe ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Promoter Activity ◽  
Critical Role ◽  
Muscle Cells ◽  
Separate Experiment ◽  
Type I

Background : Osteopontin (OPN), an extracellular matrix component produced by vascular smooth muscle cells (VSMC) and monocytes in response to biological stressors, is a regulator of cellular proliferation and migration. Recent studies revealed that OPN also plays a critical role in the progression of atherosclerotic plaques and that angiotensin II (AngII) is a potent upregulator of OPN expression. Therefore, the goal of the present study was to characterize the signaling mechanisms whereby AngII increases OPN expression. Methods and Results : YM254890, a specific inhibitor of G q/11 , potently suppressed AngII-induced OPN expression and ERK1/2 activation. Among DN mutants of small G proteins (Ras, Rac, Rho), only DN-Ras completely suppressed AngII-induced OPN promoter activity. Dominant negative (DN)-MEK1 inhibited AngII-induced OPN promoter activity by 54%, while DN-c-Jun N-terminal kinase (JNK) or DN-p38MAP kinase had no effect. DN-Src and Csk suppressed AngII-induced OPN promoter activity by 49% and 71%, respectively. In addition, small interfering RNA against Ets-1 (a transcriptional factor downstream of ERK1/2) suppressed AngII-induced OPN expression by 54 ± 4.3%. In a separate experiment, rats were treated with the AngII type I receptor blocker, valsartan (1 mg/kg/day), or vehicle for 2 weeks after carotid artery balloon injury. The intima/media ratio and OPN expression were significantly lower in valsartan-treated rats than in vehicle-treated rats. Conclusion : These data suggest that AngII-induced OPN expression in VSMC is mediated by signaling cascades involving G q/11 , the Ras-ERK axis, and c-Src, and by the transcription factor, Ets-1. Further, OPN may play a role in AngII-induced neointimal formation. These signaling molecules may represent therapeutic targets for the prevention of pathological vascular remodeling in patients with hypertension and atherosclerosis.

Migration of human vascular smooth muscle cells involves serum-dependent repeated cytosolic calcium transients

2000 ◽  
Vol 113 (4) ◽  
pp. 653-662 ◽  
Author(s):  
A. Scherberich ◽  
M. Campos-Toimil ◽  
P. Ronde ◽  
K. Takeda ◽  
A. Beretz
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Polarization ◽  
Free Calcium ◽  
Type I ◽  
Serum Dependent

Migration of vascular smooth muscle cells (VSMC) is a key event in the formation of neointima during atherosclerosis. Fura-2 loaded VSMCs were used to investigate calcium homeostasis during cell migration. Multiple spontaneous transient increases in cytosolic free calcium [Ca(2+)](i)were observed in single human VSMCs migrating on type I collagen. Such [Ca(2+)](i)transients were dependent on the presence of serum or PDGF-BB. Removal of serum, or loading cells with BAPTA, abolished the transients and decreased cell migration speed. The transients were not affected by disruption of cell polarization by dihydrocytochalasin B. Adhesion was used to investigate the specific role of cell-substrate interactions in the generation of transients. Transients are seen in VSMCs adhering either on collagen or on poly-L-lysine, suggesting that generation of transients is not strictly dependent on integrins. Buffering [Ca(2+)](i) with BAPTA led to accumulation of (beta)1 integrins at the cellular tail, and to increased release of integrin on the extracellular matrix. These results demonstrate a role for [Ca(2+)](i) transients in the rapid, serum-dependent migration of VSMCs. These [Ca(2+)](i)transients are present in migrating VSMCs only when two simultaneous events occur: (1) substrate independent spreading and (2) stimulation of cells by serum components such as PDGF-BB.

scholarly journals Lipid Incorporation Inhibits Src-Dependent Assembly of Fibronectin and Type I Collagen by Vascular Smooth Muscle Cells

2009 ◽  
Vol 104 (7) ◽  
pp. 832-841 ◽  
Author(s):  
Matthew J. Frontini ◽  
Caroline O'Neil ◽  
Cynthia Sawyez ◽  
Bosco M.C. Chan ◽  
Murray W. Huff ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Type I Collagen ◽  
Muscle Cells ◽  
Type I
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