Atorvastatin-loaded hydrogel affects the smooth muscle cells of human veins.

Details

Serval ID
serval:BIB_EB9D38B5AB2C
Type
Article: article from journal or magazin.
Collection
Publications
Title
Atorvastatin-loaded hydrogel affects the smooth muscle cells of human veins.
Journal
Journal of Pharmacology and Experimental Therapeutics
Author(s)
Dubuis C., May L., Alonso F., Luca L., Mylonaki I., Meda P., Delie F., Jordan O., Déglise S., Corpataux J.M., Saucy F., Haefliger J.A.
ISSN
1521-0103 (Electronic)
ISSN-L
0022-3565
Publication state
Published
Issued date
2013
Volume
347
Number
3
Pages
574-581
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Intimal hyperplasia (IH) is the major cause of stenosis of vein grafts. Drugs such as statins prevent stenosis, but their systemic administration has limited effects. We developed a hyaluronic acid hydrogel matrix, which ensures a controlled release of atorvastatin (ATV) at the site of injury. The release kinetics demonstrated that 100% of ATV was released over 10 hours, independent of the loading concentration of the hydrogel. We investigated the effects of such a delivery on primary vascular smooth muscle cells isolated from human veins. ATV decreased the proliferation, migration, and passage of human smooth muscle cells (HSMCs) across a matrix barrier in a similar dose-dependent (5-10 µM) and time-dependent manner (24-72 hours), whether the drug was directly added to the culture medium or released from the hydrogel. Expression analysis of genes known to be involved in the development of IH demonstrated that the transcripts of both the gap junction protein connexin43 (Cx43) and plasminogen activator inhibitor-1 (PAI-1) were decreased after a 24-48-hour exposure to the hydrogel loaded with ATV, whereas the transcripts of the heme oxygenase (HO-1) and the inhibitor of tissue plasminogen activator were increased. At the protein level, Cx43, PAI-1, and metalloproteinase-9 expression were decreased, whereas HO-1 was upregulated in the presence of ATV. The data demonstrate that ATV released from a hydrogel has effects on HSMCs similar to the drug being freely dissolved in the environment.
Pubmed
Web of science
Create date
22/12/2013 17:52
Last modification date
20/08/2019 17:13
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