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Syndecan-4 Protects...
Syndecan-4 Protects the Heart From the Profibrotic Effects of Thrombin-Cleaved Osteopontin
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- Herum, Kate M. (författare)
- Oslo university hospital,University of Oslo,Biotech Research and Innovation Centre
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- Romaine, Andreas (författare)
- University of Oslo,Oslo university hospital
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- Wang, Ariel (författare)
- University of California, San Diego
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- Melleby, Arne Olav (författare)
- Oslo university hospital,University of Oslo
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- Strand, Mari E. (författare)
- Oslo university hospital,University of Oslo
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- Pacheco, Julian (författare)
- University of California, San Diego
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- Braathen, Bjørn (författare)
- Oslo university hospital
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- Dunér, Pontus (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - matrix och inflammation i ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Matrix and Inflammation in Atherosclerosis,Lund University Research Groups
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- Tønnessen, Theis (författare)
- University of Oslo,Oslo university hospital
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- Lunde, Ida G. (författare)
- University of Oslo,Oslo university hospital
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- Sjaastad, Ivar (författare)
- University of Oslo,Oslo university hospital
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- Brakebusch, Cord (författare)
- University of Copenhagen,Biotech Research and Innovation Centre
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- McCulloch, Andrew D. (författare)
- University of California, San Diego
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- Gomez, Maria F. (författare)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Carlson, Cathrine R. (författare)
- University of Oslo,Oslo university hospital
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- Christensen, Geir (författare)
- Oslo university hospital,University of Oslo
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(creator_code:org_t)
- 2020
- 2020
- Engelska.
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 9:3, s. 013518-013518
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Pressure overload of the heart occurs in patients with hypertension or valvular stenosis and induces cardiac fibrosis because of excessive production of extracellular matrix by activated cardiac fibroblasts. This initially provides essential mechanical support to the heart, but eventually compromises function. Osteopontin is associated with fibrosis; however, the underlying signaling mechanisms are not well understood. Herein, we examine the effect of thrombin-cleaved osteopontin on fibrosis in the heart and explore the role of syndecan-4 in regulating cleavage of osteopontin. Methods and Results: Osteopontin was upregulated and cleaved by thrombin in the pressure-overloaded heart of mice subjected to aortic banding. Cleaved osteopontin was higher in plasma from patients with aortic stenosis receiving crystalloid compared with blood cardioplegia, likely because of less heparin-induced inhibition of thrombin. Cleaved osteopontin and the specific osteopontin peptide sequence RGDSLAYGLR that is exposed after thrombin cleavage both induced collagen production in cardiac fibroblasts. Like osteopontin, the heparan sulfate proteoglycan syndecan-4 was upregulated after aortic banding. Consistent with a heparan sulfate binding domain in the osteopontin cleavage site, syndecan-4 was found to bind to osteopontin in left ventricles and cardiac fibroblasts and protected osteopontin from cleavage by thrombin. Shedding of the extracellular part of syndecan-4 was more prominent at later remodeling phases, at which time levels of cleaved osteopontin were increased. Conclusions: Thrombin-cleaved osteopontin induces collagen production by cardiac fibroblasts. Syndecan-4 protects osteopontin from cleavage by thrombin, but this protection is lost when syndecan-4 is shed in later phases of remodeling, contributing to progression of cardiac fibrosis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- aortic stenosis
- cardiac fibroblasts
- extracellular matrix
- left ventricular fibrosis
- mechanical
- myofibroblast
- pressure overload
- stiffness
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Herum, Kate M.
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Romaine, Andreas
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Wang, Ariel
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Melleby, Arne Ol ...
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Strand, Mari E.
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Pacheco, Julian
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visa fler...
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Braathen, Bjørn
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Dunér, Pontus
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Tønnessen, Theis
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Lunde, Ida G.
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Sjaastad, Ivar
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Brakebusch, Cord
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McCulloch, Andre ...
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Gomez, Maria F.
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Carlson, Cathrin ...
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Christensen, Gei ...
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
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Journal of the A ...
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Lunds universitet