Copyright © 2007, European Society of Cardiology
Laminar shear stress up-regulates the expression of stearoyl-CoA desaturase-1 in vascular endothelial cells
aInstitute of Cardiovascular Science and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University, Beijing, 100083, PR China
bDepartments of Bioengineering and Medicine, University of California San Diego, La Jolla, CA 92093, USA
* Corresponding author. Institute of Cardiovascular Science, Peking University Health Science Center, Beijing 100083, China. Tel.: +86 10 82801146; fax: +86 10 82802769. Email address: npwang{at}bjmu.edu.cn
Objective: Laminar shear stress plays critical roles in vascular homeostasis and exerts various metabolic effects on endothelial cells (ECs). Stearoyl-CoA desaturase-1 (SCD1), which catalyzes the biosynthesis of monounsaturated fatty acids, affects the lipid composition and fluidity of the cell membrane. Thus, we examined the effect of laminar flow on SCD1 expression in ECs.
Methods: A flow chamber was used to impose a laminar shear stress on a confluent monolayer of human vascular ECs. The expression of SCD1 was examined using real-time RT-PCR and Northern and Western blotting. Immunohistochemical staining was used to assess the expression of SCD1 in Sprague–Dawley rat arteries, including the sites of arterial bifurcation.
Results: Laminar shear stress (12 dyn/cm2, 12 h) markedly increased the gene expression of SCD1 in ECs. The flow-induced SCD1 expression was attenuated by peroxisome proliferator-activated receptor (PPAR)-
antagonists both in vitro and in vivo. Troglitazone and rosiglitazone significantly increased the gene expression of SCD1. Furthermore, overexpression of a constitutively active PPAR induced the expression of SCD1 in ECs. Immunohistochemical study of cross-sections from rat celiac arteries revealed that endothelial expression of SCD1 was substantially higher on the medial division apex, where the shear stress is high and more laminar, than the lateral aspect, where the shear stress is low and unsteady.
Conclusion: These in vitro and in vivo results demonstrate that laminar flow increased the expression of SCD1 in endothelium through a PPAR-specific mechanism, which may contribute to the shear stress-mediated protective roles in ECs.
KEYWORDS Mechanotransduction; Hemodynamics; Endothelial functions; Gene expression; Lipid metabolism
1 These authors contributed equally to this work.
Time for primary review 39 days
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