Hypoxia-induced expression of VEGF is reversible in myocardial vascular smooth muscle cells

1997 ◽  
Vol 273 (2) ◽  
pp. H628-H633 ◽  
Author(s):  
J. W. Gu ◽  
T. H. Adair
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Conditioned Media ◽  
Dependent Manner ◽  
Induced Expression ◽  
Protein Levels

We determined whether hypoxia-induced expression of vascular endothelial growth factor (VEGF) can be reversed by a normoxic environment. Dog myocardial vascular smooth muscle cells (MVSMCs) were exposed to hypoxia (1% O2) for 24 h and then returned to normoxia (20% O2). VEGF protein levels increased by more than fivefold after 24 h of hypoxia and returned to baseline within 24 h of the return of the cells to normoxia. Northern blot analysis showed that hypoxia caused a 5.5-fold increase in VEGF mRNA, and, again, the expression was reversed after reinstitution of normoxia. Additional measurements showed that basic fibroblast growth factor and platelet-derived growth factor protein levels were not induced by hypoxia and that hypoxia caused a fourfold decrease in transforming growth factor-beta 1 protein levels. Hypoxia conditioned media from MVSMCs caused human umbilical vein endothelial cells to increase [3H]thymidine incorporation by twofold, an effect that was blocked in a dose-dependent manner by anti-human VEGF antibody. The hypoxia conditioned media had no effect on MVSMC proliferation. These findings suggest that VEGF expression can be bidirectionally controlled by tissue oxygenation, and thus support the hypothesis that VEGF is a physiological regulator of angiogenesis.

Lysophosphatidic acids induce proliferation of cultured vascular smooth muscle cells from rat aorta

1994 ◽  
Vol 267 (1) ◽  
pp. C204-C210 ◽  
Author(s):  
A. Tokumura ◽  
M. Iimori ◽  
Y. Nishioka ◽  
M. Kitahara ◽  
M. Sakashita ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Rat Aorta ◽  
Fatty Acyl ◽  
Dependent Manner ◽  
High Concentrations

Lysophosphatidic acids (LPA) with a C18 fatty acyl group accelerated thymidine incorporation into cultured rat aortic vascular smooth muscle cells and stimulated their cell division. LPA acted synergistically with epidermal growth factor and fibroblast growth factor but additively with platelet-derived growth factor. The stimulatory actions of LPA were suggested to be rather specific from the following findings: 1) their stimulation of DNA synthesis increased with an increase in their acyl moiety; 2) lysophosphatidylcholine, a neutral lysophospholipid, had no mitogenic action but was cytotoxic at high concentrations; and 3) LPA induced a rapid external Ca(2+)-independent increase in intracellular Ca2+ concentration ([Ca2+]i) in single fura 2-loaded cells that resembled the receptor-mediated increases in [Ca2+]i triggered by different agonists, whereas lysophosphatidylcholine provoked a slow sustained increase in [Ca2+]i in an external Ca(2+)-dependent manner. These results are discussed in relation to the possible pathophysiological role of LPA.

Up-regulation of Tissue Factor Expression by Platelet-derived Growth Factor in Human Vascular Smooth Muscle Cells in Culture

1997 ◽  
Vol 78 (06) ◽  
pp. 1520-1526 ◽  
Author(s):  
J M Xuereb ◽  
P Sié ◽  
B Boneu ◽  
J Constans
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Tissue Factor ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Platelet Derived Growth Factor ◽  
Dependent Manner ◽  
Dibutyryl Camp

SummaryHuman vascular smooth muscle cells (SMCs) isolated from normal adult arteries were investigated for the expression of Tissue Factor (TF) procoagulant activity at their membrane surface and TF antigen in lysed cells. In growing conditions, SMCs expressed high levels of TF activity and antigen. When cells were made quiescent by 72 h of subculture in serum-poor medium, these levels fell to about one third of the initial values. Platelet-derived growth factor BB (PDGF) up-regulated in a dose-dependent manner TF expression with a significant increase (1.8 fold) within five hours. PD 98059, a specific inhibitor of mitogen-activated protein kinase (MAPK) pathway involved in cell response to PDGF, also prevented TF up-regulation. Short-term treatment by Pentoxifylline and dibutyryl cAMP also completely prevented induced TF up-regulation, but remained without effect on baseline levels of quiescent, unstimulated cells. At their effective concentrations, pentoxifylline and dibutyryl cAMP also inhibited the activation of MAPK induced by PDGF. The rapid induction of TF upon growth factor stimulation may be important in circumstances where SMCs proliferate, such as vascular events or vessel development.

Platelet-derived growth factor stimulates Na+ influx in vascular smooth muscle cells

1984 ◽  
Vol 247 (5) ◽  
pp. C501-C505 ◽  
Author(s):  
N. E. Owen
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Platelet Derived Growth Factor ◽  
Ionophore A23187 ◽  
Dependent Manner

Platelet-derived growth factor (PDGF) is known to be a potent mitogenic agent for vascular smooth muscle cells. The effect of PDGF on amiloride-sensitive Na+ influx was investigated in A-10 vascular smooth muscle cells. At a dose which maximally stimulates DNA synthesis, PDGF stimulates net Na+ influx in vascular smooth muscle cells. The PDGF-stimulated Na+ influx is linear over a 5-min time course. PDGF stimulates Na+ influx in a concentration-dependent manner, with a concentration of 0.5 U/ml causing half-maximal inhibition. The effects of PDGF on Na+ influx can be mimicked by 10% fetal bovine serum or by the divalent cation ionophore A23187 (5 microM). Net Na+ influx in response to each of these agents was inhibited by amiloride and by benzamil. PDGF-stimulated net Na+ influx was blocked by the intracellular Ca2+ antagonist 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate as well as by the calmodulin antagonists trifluoperazine, chlorpromazine, and imipramine. These data suggest that PDGF may stimulate an amiloride-sensitive Na+ influx pathway via an elevation in intracellular Ca2+ and formation of a Ca-calmodulin complex. This Na+ influx pathway may be a trigger for PDGF-stimulated DNA synthesis.

scholarly journals CCN2 Increases TGF-β Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF-β Pathway Regulation

2021 ◽  
Vol 23 (1) ◽  
pp. 375
Author(s):  
Antonio Tejera-Muñoz ◽  
Laura Marquez-Exposito ◽  
Lucía Tejedor-Santamaría ◽  
Sandra Rayego-Mateos ◽  
Macarena Orejudo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Dependent Manner ◽  
Direct Role ◽  
Pathway Activation

The cellular communication network factor 2 (CCN2/CTGF) has been traditionally described as a mediator of the fibrotic responses induced by other factors including the transforming growth factor β (TGF-β). However, several studies have defined a direct role of CCN2 acting as a growth factor inducing oxidative and proinflammatory responses. The presence of CCN2 and TGF-β together in the cellular context has been described as a requisite to induce a persistent fibrotic response, but the precise mechanisms implicated in this relation are not described yet. Considering the main role of TGF-β receptors (TβR) in the TGF-β pathway activation, our aim was to investigate the effects of CCN2 in the regulation of TβRI and TβRII levels in vascular smooth muscle cells (VSMCs). While no differences were observed in TβRI levels, an increase in TβRII expression at both gene and protein level were found 48 h after stimulation with the C-terminal fragment of CCN2 (CCN2(IV)). Cell pretreatment with a TβRI inhibitor did not modify TβRII increment induced by CCN2(VI), demonstrating a TGF-β-independent response. Secondly, CCN2(IV) rapidly activated the SMAD pathway in VSMCs, this being crucial in the upregulation of TβRII since the preincubation with an SMAD3 inhibitor prevented it. Similarly, pretreatment with the epidermal growth factor receptor (EGFR) inhibitor erlotinib abolished TβRII upregulation, indicating the participation of this receptor in the observed responses. Our findings suggest a direct role of CCN2 maintaining the TGF-β pathway activation by increasing TβRII expression in an EGFR-SMAD dependent manner activation.

Platelet-derived growth factor regulates K-Cl cotransport in vascular smooth muscle cells

2003 ◽  
Vol 284 (3) ◽  
pp. C674-C680 ◽  
Author(s):  
Jing Zhang ◽  
Peter K. Lauf ◽  
Norma C. Adragna
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mrna Expression ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Time Dependent ◽  
Platelet Derived Growth Factor ◽  
Dependent Manner

Platelet-derived growth factor (PDGF), a potent serum mitogen for vascular smooth muscle cells (VSMCs), plays an important role in membrane transport regulation and in atherosclerosis. K-Cl cotransport (K-Cl COT/KCC), the coupled-movement of K and Cl, is involved in ion homeostasis. VSMCs possess K-Cl COT activity and the KCC1 and KCC3 isoforms. Here, we report on the effect of PDGF on K-Cl COT activity and mRNA expression in primary cultures of rat VSMCs. K-Cl COT was determined as the Cl-dependent Rb influx and mRNA expression by semiquantitative RT-PCR. Twenty four-hour serum deprivation inhibited basal K-Cl COT activity. Addition of PDGF increased total protein content and K-Cl COT activity in a time-dependent manner. PDGF activated K-Cl COT in a dose-dependent manner, both acutely (10 min) and chronically (12 h). AG-1296, a selective inhibitor of the PDGF receptor tyrosine kinase, abolished these effects. Actinomycin D and cycloheximide had no effect on the acute PDGF activation of K-Cl COT, suggesting posttranslational regulation by the drug. Furthermore, PDGF increased KCC1 and decreased KCC3 mRNA expression in a time-dependent manner. These results indicate that chronic activation of K-Cl COT activity by PDGF may involve regulation of the two KCC mRNA isoforms, with KCC1 playing a dominant role in the mechanism of PDGF-mediated activation.

Hypoxia and hypoxia-inducible factor-1α promote growth factor-induced proliferation of human vascular smooth muscle cells

2006 ◽  
Vol 290 (6) ◽  
pp. H2528-H2534 ◽  
Author(s):  
Kelly Schultz ◽  
Barry L. Fanburg ◽  
Debbie Beasley
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Hypoxia Inducible Factor ◽  
Muscle Cells ◽  
Cyclin A ◽  
Induced Expression ◽  
Moderate Hypoxia

Hypoxia is thought to be a stimulus for the excessive proliferation of vascular smooth muscle cells (VSMC) that contributes to pulmonary hypertension, but the mechanisms involved are unknown. Here we tested whether hypoxia-inducible factor 1-α (HIF-1α), a master regulator of the transcriptional response to hypoxia, is involved in the enhanced mitogen-induced proliferative responses of hypoxic VSMC. Exposure to moderate hypoxia (5% O2) enhanced the proliferative responses of human pulmonary artery SMC (HPASMC) to mitogens including platelet-derived growth factor (PDGF), fibroblast growth factor 2 (FGF-2), and epidermal growth factor (EGF), compared with those in normoxia (20% O2). Moderate hypoxia elicited increased cellular HIF-1α levels, shown by Western blot analysis, and also enhanced PDGF-, FGF-2-, and EGF-induced expression of HIF-1α. Knockdown of HIF-1α or HIF-1β levels in HPASMC with specific small interfering RNAs inhibited FGF-2-stimulated proliferation of HPASMC incubated in either 5% or 20% O2 but failed to inhibit the comitogenic effect of hypoxia. Knockdown of HIF-1α similarly inhibited PDGF-stimulated proliferation, whereas HIF-2α knockdown had no effect on HPASMC proliferation. Knockdown of HIF-1α expression also inhibited growth factor-induced expression of cyclin A. We conclude that HIF-1α promotes proliferative responses of human VSMC to FGF-2, PDGF, and EGF by mechanisms that may involve HIF-1-dependent expression of cyclin A, but HIF is apparently not crucial to the enhancement of FGF-2-, PDGF-, and EGF-induced proliferation of VSMC that occurs during hypoxia.

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