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Syndecan‐4 promotes myocardial stiffness by regulating collagen expression and cross‐linking in response to pressure overload (1152.2)
Author(s) -
Herum Kate,
Lunde Ida,
Skrbic Biljana,
Tønnessen Theis,
Louch William,
Hasic Almira,
Sjaastad Ivar,
Linke Wolfgang,
Gomez Maria,
Christensen Geir
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1152.2
Subject(s) - lysyl oxidase , pressure overload , extracellular matrix , chemistry , ventricle , hydroxyproline , medicine , matrix metalloproteinase , endocrinology , genipin , microbiology and biotechnology , heart failure , biochemistry , biology , chitosan , cardiac hypertrophy
Pressure overload of the heart leads to myocardial stiffening due to excessive production and cross‐linking of collagen, thereby compromising diastolic function. We recently identified the focal adhesion proteoglycan syndecan‐4 (syn4) as important for collagen expression in response to mechanical stress. Here we investigate the effect of syn4 deletion on the mechanical properties of the left ventricle following pressure overload. Passive tension increased in skinned muscle fiber bundles from wild‐type (WT) mice following aortic banding and this response was significantly blunted in syn4 ‐/‐ mice. Total collagen content determined by hydroxyproline quantification was increased in WT but not in syn4 ‐/‐ mice. Furthermore, mRNA levels of the collagen cross‐linking enzyme lysyl oxidase (LOX) were dramatically increased in WT left ventricles and mechanically stressed cardiac fibroblasts, whereas this response was blunted in syn4 ‐/‐ mice and cardiac fibroblasts, suggesting impaired collagen cross‐linking following mechanical stress in mice lacking syn4. Finally, recombinant extracellular syn4 and collagen I formed a precipitate when mixed in vitro , suggesting a direct role for syndecan‐4 in collagen fiber organization. In conclusion, we demonstrate reduced passive tension in left ventricular tissue of syn4 ‐/‐ mice possibly due to reduced ECM production and attenuated collagen cross‐linking. Grant Funding Source : Supported by the Norwegian Health Association and the Norwegian Research Council