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Cardiomyocyte intracellular cholesteryl ester accumulation promotes tropoelastin physical alteration and degradation: Role of LRP1 and cathepsin S.

Samouillan, Valérie and Revuelta-López, Elena and Dandurand, Jany and Nasarre, Laura and Badimon, Lina and Lacabanne, Colette and Llorente-Cortés, Vicenta Cardiomyocyte intracellular cholesteryl ester accumulation promotes tropoelastin physical alteration and degradation: Role of LRP1 and cathepsin S. (2014) The International Journal of Biochemistry & Cell Biology, 55. 209-219. ISSN 1357-2725

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Official URL: http://dx.doi.org/10.1016/j.biocel.2014.09.005


Dyslipemia has a direct impact on cardiac remodeling by altering extracellular matrix (ECM) components.One of the main ECM components is elastin, a proteic three-dimensional network that can be efficientlydegraded by cysteine proteases or cathepsins. Dyslipemic status in insulin resistance and combinedhyperlipoproteinemia diseases include raised levels of very low density lipoproteins (VLDL), triglyceride(TG)-cholesteryl ester (CE)-rich lipoproteins. Enhanced VLDL concentration promotes cardiomyocyteintracellular cholesteryl ester (CE) accumulation in a LRP1-dependent manner. The aim of this work wasto analyze the effect of cardiomyocyte intracellular CE accumulation on tropoelastin (TE) characteristicsand to investigate the role of LRP1 and cathepsin S (CatS) on these effects. Molecular studies showed thatLRP1 deficiency impaired CE selective uptake and accumulation from TG-CE-rich lipoproteins (VLDL + IDL)and CE-rich lipoproteins (aggregated LDL, agLDL). Biochemical and confocal microscopic studies showedthat LRP1-mediated intracellular CE accumulation increased CatS mature protein levels and induced analtered intracellular TE globule structure. Biophysical studies evidenced that LRP1-mediated intracellularCE accumulation caused a significant drop of Tg2 glass transition temperature of cardiomyocyte secretedTE. Moreover, CatS deficiency prevented the alterations in TE intracellular globule structure and on TEglass transition temperature. These results demonstrate that LRP1-mediated cardiomyocyte intracellularCE accumulation alters the structural and physical characteristics of secreted TE through an increase inCatS mature protein levels. Therefore, the modulation of LRP1-mediated intracellular CE accumulation incardiomyocytes could impact pathological ventricular remodeling associated with insulin-resistance andcombined hyperlipoproteinemia, pathologies characterized by enhanced concentrations of TG-CE-richlipoproteins.

Item Type:Article
Additional Information:Thanks to Elsevier editor. The definitive version is available at http://www.sciencedirect.com The original PDF of the article can be found at The International Journal of Biochemistry & Cell Biology website : http://www.sciencedirect.com/science/journal/13572725
HAL Id:hal-01112490
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
Other partners > Consejo Superior de Investigaciones Científicas - CSIC (SPAIN)
Université de Toulouse > Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UT3 (FRANCE)
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Laboratory name:
Deposited On:03 Feb 2015 09:32

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