Title: Syndecan-1 Amplifies Angiotensin II–Induced Cardiac Fibrosis
Authors: Schellings, Mark
Vanhoutte, Davy
van Almen, Geert
Swinnen, Melissa
Leenders, Joost
Kubben, Nard
Van Leeuwen, Rick
Hofstra, Leon
Heymans, Stephane
Pinto, Yigal # ×
Issue Date: 4-Feb-2010
Publisher: Lippincott Williams & Wilkins
Series Title: Hypertension vol:55 issue:2 pages:249-U87
Abstract: Syndecan-1 (Synd1) is a transmembrane heparan sulfate proteoglycan that functions as a coreceptor for various growth factors and modulates signal transduction. The present study investigated whether Synd1, by affecting growth factor signaling, may play a role in hypertension-induced cardiac fibrosis and dysfunction. Expression of Synd1 was increased significantly in mouse hearts with angiotensin II–induced hypertension, which was spatially related to cardiac fibrosis. Angiotensin II significantly impaired fractional shortening and induced cardiac fibrosis in wild-type mice, whereas these effects were blunted in Synd1-null mice. Angiotensin II significantly increased cardiac expression of connective tissue growth factor and collagen type I and III in wild-type mice, which was blunted in Synd1-null mice. These findings were confirmed in vitro, where angiotensin II induced the expression of both connective tissue growth factor and collagen I in fibroblasts. The absence of Synd1 in either Synd1-null fibroblasts, after knockdown of Synd1 by short hairpin RNA, or after inhibition of heparan sulfates by protamine attenuated this increase, which was associated with reduced phosphorylation of Smad2. In conclusion, loss of Synd1 reduces cardiac fibrosis and dysfunction during angiotensin II–induced hypertension.
ISSN: 0194-911X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Cardiology
Molecular and Vascular Biology
× corresponding author
# (joint) last author

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