Effects of smooth muscle cell derived growth factor (SDGF) in combination with other growth factors on smooth muscle cells

Vascular smooth muscle cell proliferation has been shown to be an important factor in atheromatous plaque formation, hypertrophy associated with essential hypertension, and failure of balloon angioplasty procedures. Investigators have shown that a number of different agents stimulate vascular smooth muscle cell proliferation, including epidermal growth factor, platelet-derived growth factor, angiotensin II, and catecholamines. Previously, we have demonstrated that these agents also cause immediate changes in ion transport and second messenger generation in vascular smooth muscle cells. We have proposed that these immediate changes may be linked to each other and to cell proliferation. In contrast to the many agents that have been shown to stimulate vascular smooth muscle cell proliferation, only a few agents (e.g., heparin sodium or transforming growth factor-beta) have been shown to inhibit vascular smooth muscle cell proliferation. In the present study we have investigated whether heparin inhibits serum- or growth factor-stimulated changes in ion transport and second messenger generation in vascular smooth muscle cells. We found that heparin inhibits serum- or growth factor-stimulated Na(+)-H+ exchange in a concentration-dependent manner that is not dependent on the ability of heparin to function as an anticoagulant agent. In addition, other glycosaminoglycans were not found to be inhibitory, and the inhibitory effects of heparin were discovered to be limited to vascular smooth muscle cells. Heparin does not appear to be acting by binding to growth factors, or by directly inhibiting the Na(+)-H+ exchange protein. However, heparin did inhibit serum- or growth factor-stimulated inositol trisphosphate release and calcium mobilization.(ABSTRACT TRUNCATED AT 250 WORDS)

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Involvement of Cyclooxygenase- and Lipoxygenase-Mediated Conversion of Arachidonic Acid in Controlling Human Vascular Smooth Muscle Cell Proliferation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1645212 ◽

1990 ◽

Vol 63 (02) ◽

pp. 291-297 ◽

Cited By ~ 28

Author(s):

Herm-Jan M Brinkman ◽

Marijke F van Buul-Worteiboer ◽

Jan A van Mourik

Keyword(s):

Cell Proliferation ◽

Arachidonic Acid ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Vascular Smooth Muscle Cell ◽

Muscle Cells ◽

Smooth Muscle Cell Proliferation

SummaryWe observed that the growth of human umbilical arterysmooth muscle cells was inhibited by the phospholipase A2 inhibitors p-bromophenacylbromide and mepacrine. Thesefindings suggest that fatty acid metabolism might be integrated in the control mechanism of vascular smooth muscle cell proliferation. To identify eicosanoids possibly involved in this process, we studied both the metabolism of arachidonic acid of these cells in more detail and the effect of certain arachidonic acid metabolites on smooth muscle cells growth. We found no evidence for the conversion of arachidonic acid via the lipoxygenase pathway. In contrast, arachidonic acid was rapidly converted via the cyclooxy-genase pathway. The following metabolites were identified: prostaglandin E2 (PGE2), 6-keto-prostaglandin F1α (6-k-PGF1α), prostaglandin F2α (PGF2α), 12-hydroxyheptadecatrienoic acid (12-HHT) and 11-hydroxyeicosatetetraenoic acid (11-HETE). PGE2 was the major metabolite detected. Arachidonic acid metabolites were only found in the culture medium, not in the cell. After synthesis, 11-HETE was cleared from the culture medium. We have previously reported that PGE2 inhibits the serum-induced [3H]-thymidine incorporation of growth-arrested human umbilical artery smooth muscle cells. Here we show that also 11-HETEexerts this inhibitory property. Thus, our data suggeststhat human umbilical artery smooth muscle cells convert arachidonic acid only via the cyclooxygenase pathway. Certain metabolites produced by this pathway, including PGE2 and 11-HETE, may inhibit vascular smooth muscle cell proliferation.

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Hydrogen sulfide dilates cerebral arterioles by activating smooth muscle cell plasma membrane KATP channels

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01290.2010 ◽

2011 ◽

Vol 300 (6) ◽

pp. H2088-H2095 ◽

Cited By ~ 41

Author(s):

Guo Hua Liang ◽

Adebowale Adebiyi ◽

M. Dennis Leo ◽

Elizabeth M. McNally ◽

Charles W. Leffler ◽

...

Keyword(s):

Smooth Muscle ◽

Hydrogen Sulfide ◽

Smooth Muscle Cells ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Muscle Cells ◽

Mass Spectrometry Data ◽

Vascular Regulation ◽

Cerebral Arterioles ◽

Cerebral Arteriole

Hydrogen sulfide (H2S) is a gaseous signaling molecule that appears to contribute to the regulation of vascular tone and blood pressure. Multiple potential mechanisms of vascular regulation by H2S exist. Here, we tested the hypothesis that piglet cerebral arteriole smooth muscle cells generate ATP-sensitive K+ (KATP) currents and that H2S induces vasodilation by activating KATP currents. Gas chromatography/mass spectrometry data demonstrated that after placing Na2S, an H2S donor, in solution, it rapidly (1 min) converts to H2S. Patch-clamp electrophysiology indicated that pinacidil (a KATP channel activator), Na2S, and NaHS (another H2S donor) activated K+ currents at physiological steady-state voltage (−50 mV) in isolated cerebral arteriole smooth muscle cells. Glibenclamide, a selective KATP channel inhibitor, fully reversed pinacidil-induced K+ currents and partially reversed (∼58%) H2S-induced K+ currents. Western blot analysis indicated that piglet arterioles expressed inwardly rectifying K+ 6.1 (Kir6.1) channel and sulfonylurea receptor 2B (SUR2B) KATP channel subunits. Pinacidil dilated pressurized (40 mmHg) piglet arterioles, and glibenclamide fully reversed this effect. Na2S also induced reversible and repeatable vasodilation with an EC50 of ∼30 μM, and this effect was partially reversed (∼55%) by glibenclamide. Vasoregulation by H2S was also studied in pressurized resistance-size cerebral arteries of mice with a genetic deletion in the gene encoding SUR2 (SUR2 null). Pinacidil- and H2S-induced vasodilations were smaller in arterioles of SUR2 null mice than in wild-type controls. These data indicate that smooth muscle cell KATP currents control newborn cerebral arteriole contractility and that H2S dilates cerebral arterioles by activating smooth muscle cell KATP channels containing SUR2 subunits.

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Effects of hypoxia on rat airway smooth muscle cell proliferation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00363.2002 ◽

2003 ◽

Vol 94 (4) ◽

pp. 1403-1409 ◽

Cited By ~ 21

Author(s):

A. Cogo ◽

G. Napolitano ◽

M. C. Michoud ◽

D. Ramos Barbon ◽

M. Ward ◽

...

Keyword(s):

Cell Proliferation ◽

Smooth Muscle ◽

Cell Growth ◽

Smooth Muscle Cells ◽

Smooth Muscle Cell ◽

Airway Smooth Muscle ◽

Muscle Cell ◽

Muscle Cells ◽

Airway Smooth Muscle Cell ◽

Gf 109203X

Although it is well known that hypoxemia induces pulmonary vasoconstriction and vascular remodeling, due to the proliferation of both vascular smooth muscle cells and fibroblasts, the effects of hypoxemia on airway smooth muscle cells are not well characterized. The present study was designed to assess the in vitro effects of hypoxia (1 or 3% O2) on rat airway smooth muscle cell growth and response to mitogens (PDGF and 5-HT). Cell growth was assessed by cell counting and cell cycle analysis. Compared with normoxia (21% O2), there was a 42.2% increase in the rate of proliferation of cells exposed to 3% O2 (72 h, P = 0.006), as well as an enhanced response to PDGF (13.9% increase; P = 0.023) and to 5-HT (17.2% increase; P = 0.039). Exposure to 1% O2 (72 h) decreased cell proliferation by 21.0% ( P = 0.017) and reduced the increase in cell proliferation induced by PGDF and 5-HT by 16.2 and 15.7%, respectively ( P = 0.019 and P = 0.011). A significant inhibition in hypoxia-induced cell proliferation was observed after the administration of bisindolylmaleimide GF-109203X (a specific PKC inhibitor) or downregulation of PKC with PMA. Pretreatment with GF-109203X decreased proliferation by 21.5% ( P = 0.004) and PMA by 31.5% ( P = 0.005). These results show that hypoxia induces airway smooth muscle cell proliferation, which is at least partially dependent on PKC activation. They suggest that hypoxia could contribute to airway remodeling in patients suffering from chronic, severe respiratory diseases.

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Airway smooth muscle proliferation and inflammation in asthma

Journal of Applied Physiology ◽

10.1152/japplphysiol.00342.2018 ◽

2018 ◽

Vol 125 (4) ◽

pp. 1090-1096 ◽

Cited By ~ 8

Author(s):

Alan L. James ◽

Peter B. Noble ◽

Su-Ann Drew ◽

Thais Mauad ◽

Tony R. Bai ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Smooth Muscle Cell ◽

Airway Inflammation ◽

Cell Size ◽

Airway Smooth Muscle ◽

Muscle Cell ◽

Muscle Cells ◽

Muscle Layer ◽

Airway Smooth Muscle Cells

In asthma, it is unclear if the airway smooth muscle cells proliferate more or are increased at the onset of asthma and remain stable. This study aimed to compare smooth muscle cell proliferation in individuals with and without asthma and correlate proliferation rates with cell size and number and with granulocytic airway inflammation. Postmortem airway sections were labeled with proliferating cell nuclear antigen (PCNA) and percent positive muscle cells calculated. On the same sections, smooth muscle cell size and number and the number of eosinophils and neutrophils were estimated and compared in cases of nonfatal ( n = 15) and fatal ( n = 15) asthma and control subjects ( n = 15). The %PCNA+ muscle cells was not significantly different in fatal (29.4 ± 7.7%, mean ± SD), nonfatal asthma (28.6 ± 8.3%), or control subjects (24.6 ± 6.7%) and not related to mean muscle cell size ( r = 0.09), number ( r = 0.36), thickness of the muscle layer ( r = 0.05), or eosinophil numbers ( r = 0.04) in the asthma cases. These data support the hypothesis that in asthma the increased thickness of the smooth muscle layer may be present before or at the onset of asthma and independent of concurrent granulocytic inflammation or exacerbation. NEW & NOTEWORTHY There is debate regarding the origins of the increased airway smooth muscle in asthma. It may be independent of inflammation or arise as a proliferative response to inflammation. The present study found no increase in the proportion of proliferating smooth muscle cells in asthma and no relation of proliferation to numbers of airway smooth muscle cells or inflammation. These results support a stable increase in smooth muscle in asthma that is independent of airway inflammation.

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Cyclic Mechanical Stretch Induced Smooth Muscle Cell Changes in Cerebral Aneurysm Progress by Reducing Collagen Type IV and Collagen Type VI Levels

Cellular Physiology and Biochemistry ◽

10.1159/000487347 ◽

2018 ◽

Vol 45 (3) ◽

pp. 1051-1060 ◽

Cited By ~ 7

Author(s):

Peixi Liu ◽

Yaying Song ◽

Yingjie Zhou ◽

Yingjun Liu ◽

Tianming Qiu ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Collagen Type ◽

Cerebral Aneurysms ◽

Muscle Cells ◽

Mechanical Stretch ◽

Collagen Type Iv ◽

Type Iv

Background/Aims: Cerebral aneurysm growth is characterized by continuous structural weakness of local smooth muscle cells, though the mechanism is unclear. In this study, we examine protein changes in cerebral aneurysm and human brain vascular smooth muscle cells after cyclic mechanical stretch. We further explore the relationship between the smooth muscle cell changes and reductions in the levels of collagen types IV and VI. Methods: Saccular cerebral aneurysms (n=10) were collected, and temporal artery samples were used as controls. Quantitative proteomics were analyzed and histopathological changes were examined. Smooth muscle cells were cultured in a flexible silicone chamber and subjected to 15% cyclic mechanical stretch. The effect of stretch on the cell viability, function, gene and protein expression were further studied for the understanding the molecular mechanism of aneurysm development. Results: Proteomics analysis revealed 92 proteins with increased expression and 88 proteins with decreased expression compared to the controls (p<0.05). KEGG pathway analysis showed that the change in focal adhesion and extracellular matrix-receptor interaction, suggesting the involvement of collagen type IV and VI. The aneurysm tissue exhibited fewer smooth muscle cells and lower levels of collagen type IV and VI. Human brain vascular smooth muscle cell culture showed spindle-like cells and obvious smooth muscle cell layer. Cell proteomics analysis showed that decreased expression of 118 proteins and increased expression of 32 proteins in smooth muscle cells after cyclic mechanical stretch. KEGG pathway analysis indicated that focal adhesion and ECM-receptor interaction were involved. After cyclic mechanical stretch, collagen type IV and IV expression were decreased. Moreover, the stretch induced MMP-1 and MMP-3 expression elevation. Conclusion: We demonstrated that collagen type IV and VI were decreased in cerebral aneurysms and continuous cyclic mechanical stretch induced smooth muscle cell changes. Smooth muscle cell protection provides an additional therapeutic option to prevent the growth of cerebral aneurysms.

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Multiple neuropeptides exert a direct effect on the same isolated single smooth muscle cell

AJP Cell Physiology ◽

10.1152/ajpcell.1986.250.5.c792 ◽

1986 ◽

Vol 250 (5) ◽

pp. C792-C798 ◽

Cited By ~ 20

Author(s):

N. L. Lassignal ◽

J. J. Singer ◽

J. V. Walsh

Keyword(s):

Smooth Muscle ◽

Substance P ◽

Smooth Muscle Cells ◽

Smooth Muscle Cell ◽

Vasoactive Intestinal Peptide ◽

Direct Effect ◽

Muscle Cell ◽

Muscle Cells ◽

Cholecystokinin Octapeptide ◽

Single Smooth Muscle Cell

The contractile effect of various neuropeptides was examined by pressure ejecting these agents from a pipette onto single smooth muscle cells freshly dissociated from the stomach of Bufo marinus. Substance P, cholecystokinin-octapeptide, and bombesin caused contraction, whereas vasoactive intestinal peptide, secretin, and dopamine inhibited acetylcholine-induced contractions. Acetylcholine and the three peptides which produced contraction were found in some instances to act on the same cell, suggesting that receptors for these agents exist on one and the same cell.

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