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LRP5/canonical Wnt signalling and healing of ischemic myocardium

Borrell-Pages, M., Vilahur, G., Romero, J. C., Casaní, L., Bejar, M. T., Badimon, L.·2016·Basic Research in Cardiology
DOI 10.1007/s00395-016-0585-y
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Abstract

LRP5 (low-density lipoprotein receptor-related protein 5) activates canonical Wnt signalling. LRP5 plays multiple roles including regulation of lipoprotein and cholesterol homeostasis as well as innate immunity cell function. However, it is not known whether LRP5 has a role in the myocardium. The aim of this study was to investigate LRP5 and Wnt signalling in myocardial remodelling after acute myocardial infarction (MI). Wnt protein levels were determined in a hypercholesterolemic porcine model of MI, in Lrp5 -/- C57Bl6 mice, in cultured cardiomyocytes and in human explanted hearts with previous MI episodes. 21 days post-MI, there was upregulation of LRP5 in the ischemic myocardium of hypercholesterolemic pigs as well as an upregulated expression of proteins of the Wnt pathway. We demonstrate via overexpression and silencing experiments that LRP5 induces Wnt pathway activation in isolated cardiomyocytes. Hypoxia and lipid-loading induced the expression of Wnt proteins, whereas this effect is blocked in LRP5-silenced cardiomyocytes. To characterize the function of the LRP5-Wnt axis upregulation in the heart, we induced MI in wild-type and Lrp5 -/- mice. Lrp5 -/- mice had significantly larger infarcts than Wt mice, indicating a protective role of LRP5 in injured myocardium. The LRP5 upregulation in post-MI hearts seen in pigs and mice was also evident in human hearts as dyslipidemic patients with previous episodes of ischemia have higher expression of LRP5 and Wnt-signalling ge…

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Authors
Borrell-Pages, M., Vilahur, G., Romero, J. C., Casaní, L., Bejar, M. T., & Badimon, L.
ORCID
Badimon, L.
Venue
Basic Research in Cardiology
Publisher
Springer Science and Business Media LLC
Published
2016-10-04
Volume
111
Issue
6
ISSN
  • 0300-8428
  • 1435-1803
DOI
10.1007/s00395-016-0585-y
Cited by
31
References
2
Language
en
Licence
www.springer.com/tdm (unspecified)
Funders
  • Spanish Ministry of Economy and Competitiveness (Plan Estatal I+D+I 2013-2016, SAF2013-42962-R, SAF2012-40208)
  • Instituto de Salud Carlos III (ES) (TERCEL RD12/0019/0026)
  • Institute of Health Carlos III, (RIC RD12/0042/0027)
  • Sociedad Española de Cardiología (SEC 2015)

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