scholarly journals The effect of trinitrobenzene sulfonic acid on gut-derived smooth muscle cell arachidonic acid metabolism: role of endogenous prostanoids

1997 ◽  
Vol 6 (3) ◽  
pp. 237-240
Author(s):  
W. E. Longo ◽  
G. S. Smith ◽  
Y. Deshpande ◽  
C. Reickenberg ◽  
D. L. Kaminski
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Sulfonic Acid ◽  
Muscle Cells ◽  
Arachidonic Acid Metabolism ◽  
Trinitrobenzene Sulfonic Acid ◽  
Eicosanoid Production

The contribution of smooth muscle cells as a potential source of eicosanoid production during inflammatory states remains to be elucidated. We investigated the effect of trinitrobenzene sulfonic acid (TNB), a known pro-inflammatory agent, on jejunal smooth muscle cell eicosanoid production. Human gut-derived smooth muscle cells (HISM) were incubated with TNB for 1 hour. Additionally, some cells were preincubated with either dimethylthiourea, or indomethacin for 1 hour before exposure to identical concentrations of TNB. Incubation with TNB led to significant increases in PGE2and 6-keto PGF-1αrelease, but not leukotriene B4release; responses which were both inhibited by dimethylthiourea and indomethacin treatment. Our results suggest that gutderived smooth muscle cells may represent an important source of proinflammatory prostanoids but not leukotrienes during inflammatory states of the intestine. The inhibition of prostanoid activity by thiourea may be mediated by suppression of cyclooxygenase activity in this cell line.

scholarly journals Epac1 is upregulated during neointima formation and promotes vascular smooth muscle cell migration

2008 ◽  
Vol 295 (4) ◽  
pp. H1547-H1555 ◽  
Author(s):  
Utako Yokoyama ◽  
Susumu Minamisawa ◽  
Hong Quan ◽  
Toru Akaike ◽  
Meihua Jin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Remodeling ◽  
Muscle Cells ◽  
Smooth Muscle Cell Migration

Vascular remodeling after mechanoinjury largely depends on the migration of smooth muscle cells, an initial key step to wound healing. However, the role of the second messenger system, in particular, the cAMP signal, in regulating such remodeling remains controversial. Exchange protein activated by cAMP (Epac) has been identified as a new target molecule of the cAMP signal, which is independent from PKA. We thus examined whether Epac plays a distinct role from PKA in vascular remodeling. To examine the role of Epac and PKA in migration, we used primary culture smooth muscle cells from both the fetal and adult rat aorta. A cAMP analog selective to PKA, 8-(4-parachlorophenylthio)-cAMP (pCPT-cAMP), decreased cell migration, whereas an Epac-selective analog, 8-pCPT-2′- O-Me-cAMP, enhanced migration. Adenovirus-mediated gene transfer of PKA decreased cell migration, whereas that of Epac1 significantly enhanced cell migration. Striking morphological differences were observed between pCPT-cAMP- and 8-pCPT-2′- O-Me-cAMP-treated aortic smooth muscle cells. Furthermore, overexpression of Epac1 enhanced the development of neointimal formation in fetal rat aortic tissues in organ culture. When the mouse femoral artery was injured mechanically in vivo, we found that the expression of Epac1 was upregulated in vascular smooth muscle cells, whereas that of PKA was downregulated with the progress of neointimal thickening. Our findings suggest that Epac1, in opposition to PKA, increases vascular smooth muscle cell migration. Epac may thus play an important role in advancing vascular remodeling and restenosis upon vascular injury.

scholarly journals Abl regulates smooth muscle cell proliferation by modulating actin dynamics and ERK1/2 activation

2012 ◽  
Vol 302 (7) ◽  
pp. C1026-C1034 ◽  
Author(s):  
Li Jia ◽  
Ruping Wang ◽  
Dale D. Tang
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Actin Polymerization ◽  
Muscle Cells ◽  
Smooth Muscle Cell Proliferation ◽  
Actin Dynamics

Abl is a nonreceptor tyrosine kinase that has a role in regulating migration and adhesion of nonmuscle cells as well as smooth muscle contraction. The role of Abl in smooth muscle cell proliferation has not been investigated. In this study, treatment with endothelin-1 (ET-1) and platelet-derived growth factor (PDGF) increased Abl phosphorylation at Tyr412 (an indication of Abl activation) in vascular smooth muscle cells. To assess the role of Abl in smooth muscle cell proliferation, we generated stable Abl knockdown cells by using lentivirus-mediated RNA interference. ET-1- and PDGF-induced cell proliferation was attenuated in Abl knockdown cells compared with cells expressing control shRNA and uninfected cells. Abl silencing also arrested cell cycle progression from G0/G1 to S phase. Furthermore, activation of smooth muscle cells with ET-1 and PDGF induced phosphorylation of ERK1/2 and Akt. Abl knockdown attenuated ERK1/2 phosphorylation in smooth muscle cells stimulated with ET-1 and PDGF. However, Akt phosphorylation upon stimulation with ET-1 and PDGF was not reduced. Because Abl is known to regulate actin polymerization in smooth muscle, we also evaluated the effects of inhibition of actin polymerization on phosphorylation of ERK1/2. Pretreatment with the actin polymerization inhibitor latrunculin-A also blocked ERK1/2 phosphorylation during activation with ET-1 and PDGF. The results suggest that Abl may regulate smooth muscle cell proliferation by modulating actin dynamics and ERK1/2 phosphorylation during mitogenic activation.

scholarly journals The roles of mechanotransduction, vascular wall cells, and blood cells in atheroma induction

Vascular ◽  
2018 ◽  
Vol 27 (1) ◽  
pp. 98-109 ◽  
Author(s):  
Olga A Novikova ◽  
Pavel P Laktionov ◽  
Andrey A Karpenko
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Molecular Mechanisms ◽  
Muscle Cells ◽  
Phenotypic Switching ◽  
Atheromatous Plaque ◽  
Atheromatous Plaques

Background This paper describes and analyzes the cellular and molecular mechanisms underlying atherosclerosis development. In particular, the roles of monocytes/macrophages, smooth muscle cells, and vascular endothelium in the formation of stable/unstable atheromatous plaques, and the contributions of some processes to atheroma formation. Methods and results In this study we analyzed endothelium: function, dysfunction, and involvement into atherogenesis; cell proteins mediating mechanotransduction; proatherogenic role of monocytes; the role of macrophages in the development of unstable atheromatous plaques and smooth muscle cell origin in atherosclerosis. Smooth muscle cell phenotypic switching; their functioning; the ability to retain cholesterol and lipoproteins as well as secretion of pro- and anti-inflammatory molecules and extracellular matrix proteins, their response to extracellular stimuli secreted by other cells, and the effect of smooth muscle cells on the cells surrounding atheromatous plaques are fundamentally important for the insight into atherosclerosis molecular basis. Conclusion Atheromatous plaque transcriptome studies will be helpful in the identification of the key genes involved in atheroma transformation and development as well as discovery of the new targets for diagnosis and therapy.

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

1990 ◽  
Vol 63 (02) ◽  
pp. 291-297 ◽  
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.

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

2011 ◽  
Vol 300 (6) ◽  
pp. H2088-H2095 ◽  
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.

Effects of hypoxia on rat airway smooth muscle cell proliferation

2003 ◽  
Vol 94 (4) ◽  
pp. 1403-1409 ◽  
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.

scholarly journals Airway smooth muscle proliferation and inflammation in asthma

2018 ◽  
Vol 125 (4) ◽  
pp. 1090-1096 ◽  
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.

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

2018 ◽  
Vol 45 (3) ◽  
pp. 1051-1060 ◽  
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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