Abstract:
:Autologous venous grafts, used to circumvent occluded coronary arteries during coronary artery bypass, often develop thrombosis and neointimal hyperplasia. During neointimal hyperplasia, vascular smooth muscle cells (VSMCs), exposed to substantially higher pressure and hemodynamic forces, proliferate and extracellular matrix accumulate causing narrowing of the vessel lumen. Activation of insulin-like growth factor-1 receptor (IGF-1R) has been confirmed to be critically involved in mechanical stretch-stimulated VSMC proliferation. However, the comprehensive mechanisms responsible for activation of IGF-1R in VSMCs by mechanical stretch remain unclear. This study found that miR-223 and miR-153, targeted to IGF-1R, were down-regulated in VSMCs under stretch stress by miRNA microarray analysis in conjunction with Target Scan analysis. Overexpression of miR-223 or miR-153 down-regulated IGF-1R expression and activity in VSMCs under stretch stress. Specifically, overexpression of miR-223 and miR-153 inhibited stretch stress-enhanced VSMC proliferation and the activity of PI3K-AKT signaling. In conclusion, our study indicates that miR-153 and miR-223 are reduced in VSMCs by stretch stress, contributing to IGF-1R activation and resultant VSMC proliferation. Thus, miR-153 and miR-223 may be viable therapeutic targets for mechanical stretch-induced neointimal hyperplasia in vein grafts.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Song L,Duan P,Guo P,Li D,Li S,Xu Y,Zhou Qdoi
10.1016/j.abb.2012.08.015subject
Has Abstractpub_date
2012-12-15 00:00:00pages
204-11issue
2eissn
0003-9861issn
1096-0384pii
S0003-9861(12)00332-3journal_volume
528pub_type
杂志文章abstract::In the present study, using the C24 bile acid chenodeoxycholic acid as substrate, rat liver bile acid CoA ligase activity (rBAL) was purified 200-fold from detergent-solubilized microsomes using a combination of Q-Sepharose anion exchange, hydroxyapatite, and CM-Sepharose chromatography. Purified rBAL had a molecular ...
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2000-12-15 00:00:00
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