scholarly journals The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease

2009 ◽  
Vol 16 (12) ◽  
pp. 1590-1598 ◽  
Author(s):  
L Elia ◽  
M Quintavalle ◽  
J Zhang ◽  
R Contu ◽  
L Cossu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Human Disease ◽  
Vascular Homeostasis ◽  
Cell Maintenance

Abstract 5495: Role of SIRT1 in Smooth Muscle Cell Function and Vascular Remodeling

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Daniel Sedding ◽  
Sabina Vogel ◽  
Harald Tillmanns
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Cell Function ◽  
Model Organisms ◽  
Dependent Manner ◽  
Wild Type ◽  
Vascular Homeostasis

Background: The class III histone deacetylase SIRT1 has been identified as a key regulator of ageing and longevity in model organisms such as S. cerevisiae and C. elegans, which regulates cellular functions such as differentiation, senescence and metabolism. However, the role of SIRT1 for Smooth muscle cell (VSMC) function and vascular homeostasis or during vascular remodelling remains unknown. Methods and Results: Here, we show that SIRT1 is highly expressed in intact blood vessels in vivo as well as in cultured VSMC. Stimulation of SIRT1 activity by either treatment with the SIRT1 activator resveratrol or adenoviral overexpression of wild type SIRT1 but not with an inactive SIRT1 mutant attenuated serum-induced VSMC proliferation in a dose dependent manner in vitro. In contrast, treatment of VSMC with the small molecule weight inhibitors of SIRT1, nicotinamide and sirtinol, augmented the proliferative and migratory activity of VSMC. Consistent with these data, MEF cells isolated from SIRT −/− mice showed an augmented proliferative response to serum stimulation but were also more resistant to starving-induced apoptosis compared to WT-MEF cells. Silencing of endogenous SIRT1 using siRNA resulted in an increased proliferation, migration and apoptosis of VSMC. In vivo, following arterial injury of the mouse femoral artery, SIRT1 was downregulated in the developing neointima. Adenoviral-mediated reconstitution of wild type SIRT1 but not of the inactive SIRT1 mutant prevented neointima formation in vivo. Conclusion: Thus, these data identify SIRT1 as a key regulator of vascular proliferative disease processes and indicate that SIRT1 plays an essential role in proliferative migratory and apoptotic processes which regulate vascular homeostasis and remodeling.

Intestinal Smooth Muscle Cell Maintenance by Basic Fibroblast Growth Factor

2008 ◽  
Vol 14 (8) ◽  
pp. 1395-1402 ◽  
Author(s):  
Min Lee ◽  
Benjamin M. Wu ◽  
Matthias Stelzner ◽  
Holger M. Reichardt ◽  
James C.Y. Dunn
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cell ◽  
Fibroblast Growth Factor ◽  
Muscle Cell ◽  
Basic Fibroblast Growth Factor ◽  
Intestinal Smooth Muscle ◽  
Fibroblast Growth ◽  
Cell Maintenance

1429: Upregulation of Rho-Kinase in a Human Corpus Cavernosum Smooth Muscle Cell Line in Response to Hypoxia

2004 ◽  
Vol 171 (4S) ◽  
pp. 376-377
Author(s):  
Yongmu Zheng ◽  
Shaohua Chang ◽  
Alan J. Wein ◽  
Samuel Chacko ◽  
Michael E. DiSanto
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Cell Line ◽  
Muscle Cell ◽  
Corpus Cavernosum ◽  
Rho Kinase ◽  
Muscle Cell Line

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.

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