Background and aims Vascular biglycan contributes to atherosclerosis development and increased biglycan expression correlates with increased atherosclerosis. However, mice deficient in biglycan have either no reduction in atherosclerosis or an unexpected increase in atherosclerosis. Biglycan deficient mice have systemically elevated TGF-β, likely due to lack of sequestration of TGF-β in the extracellular matrix. The purpose of this study was to determine if prevention of TGF-β elevations in biglycan deficient mice affected atherosclerosis development. Methods Biglycan deficient mice were crossed to Ldlr deficient mice. Diabetes was induced via streptozotocin and all mice were fed a high cholesterol diet. Diabetic biglycan wild type and biglycan deficient Ldlr deficient mice were injected with the TGF-β neutralizing antibody 1D11 or the irrelevant control antibody 13C4. Results Biglycan deficient mice had significantly elevated plasma TGF-β levels, which was further increased by diabetes, and significantly increased atherosclerosis. There was a significant correlation between TGF-β concentrations and atherosclerosis. However, despite nearly complete suppression of plasma TGF-β levels in mice treated with the TGF-β neutralizing antibody 1D11, there was no significant difference in atherosclerosis between mice with elevated TGF-β levels and mice with suppressed TGF-β levels. Conclusions The increased atherosclerosis in biglycan deficient mice does not appear to be due to elevations in TGF-β.
|Number of pages||8|
|State||Published - Jan 2018|
Bibliographical noteFunding Information:
This work was supported by Merit Review Award BX000622 to LRT from the Department of Veterans Affairs, and used Cores supported by NIH P30 GM103527 . The contents of this publication are solely the responsibility of the authors and do not represent the views of the National Institutes of Health, the Department of Veterans Affairs or the United States Government.
- Animal models
- Extracellular matrix
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine