UNIGE document Scientific Article
previous document  unige:31881  next document
add to browser collection
Title

Atorvastatin-Loaded Hydrogel Affects the Smooth Muscle Cells of Human Veins

Authors
Dubuis, C.
May, L.
Alonso, F.
show hidden authors show all authors [1 - 12]
Published in Journal of Pharmacology and Experimental Therapeutics. 2013, vol. 347, no. 3, p. 574-581
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 dosedependent (5–10 mM) 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.
Keywords Vascular stenosisDrug deliveryAtorvastatinHydrogelSmooth muscle cells
Identifiers
Full text
Structures
Citation
(ISO format)
DUBUIS, C. et al. Atorvastatin-Loaded Hydrogel Affects the Smooth Muscle Cells of Human Veins. In: Journal of Pharmacology and Experimental Therapeutics, 2013, vol. 347, n° 3, p. 574-581. https://archive-ouverte.unige.ch/unige:31881

244 hits

2 downloads

Update

Deposited on : 2013-12-09

Export document
Format :
Citation style :