Journal
ATHEROSCLEROSIS
Volume 195, Issue 1, Pages 23-30Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2006.11.023
Keywords
restenosis; arterial smooth muscle cells; Sirolimus; hyaluronan; monocytes
Funding
- NHLBI NIH HHS [P01 HL018645-300008, P01 HL-18645-30, P01 HL018645] Funding Source: Medline
Ask authors/readers for more resources
Sirolimus (SRL), an inhibitor of human arterial smooth muscle cell (ASMC) proliferation and migration, prevents in-stent restenosis (ISR). Little is known about the effect of SRL on the extracellular matrix (ECM) component, hyaluronan, a key macromolecule in neointimal hyperplasia and inflammation. In this study, we investigated SRL regulation of the synthesis of hyaluronan by cultured human ASMC and the effect of SRL on hyaluronan mediated monocyte adhesion to the ECM. Hyaluronan production on a per cell basis was significantly inhibited by SRL at 4 days and remained so through 10 days. This reduction was correlated with reduced levels of hyaluronan synthase mRNAs while hyaluronan degradation rates were unchanged. Poly I:C, a viral mimetic, caused increased hyaluronan accumulation by ASMC cell layers and this increase was inhibited by SRL. The inhibition was paralleled by a reduction in hyaluronan-dependent monocyte adhesion to the ECM. This study demonstrates that SRL not only regulates the proliferation of ASMC but reduces the production of hyaluronan by these cells. This alteration in ECM composition results in reduced monocyte adhesion to the ECM in cultures of ASMC. Alterations in hyaluronan accumulation may contribute to the inhibition of ISR that is achieved by SRL. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available