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Página principal > Artículos > Artículos publicados > Relationship among LRP1 expression, Pyk2 phosphorylation and MMP-9 activation in left ventricular remodelling after myocardial infarction |
Fecha: | 2017 |
Resumen: | Left ventricular (LV) remodelling after myocardial infarction (MI) is a crucial determinant of the clinical course of heart failure. Matrix metalloproteinase (MMP) activation is strongly associated with LV remodelling after MI. Elucidation of plasma membrane receptors related to the activation of specific MMPs is fundamental for treating adverse cardiac remodelling after MI. The aim of current investigation was to explore the potential association between the low-density lipoprotein receptor-related protein 1 (LRP1) and MMP-9 and MMP-2 spatiotemporal expression after MI. Real-time PCR and Western blot analyses showed that LRP1 mRNA and protein expression levels, respectively, were significantly increased in peri-infarct and infarct zones at 10 and 21 days after MI. Confocal microscopy demonstrated high colocalization between LRP1 and the fibroblast marker vimentin, indicating that LRP1 is mostly expressed by cardiac fibroblasts in peri-infarct and infarct areas. LRP1 also colocalized with proline-rich tyrosine kinase 2 (pPyk2) and MMP-9 in cardiac fibroblasts in ischaemic areas at 10 and 21 days after MI. Cell culture experiments revealed that hypoxia increases LRP1, pPyk2 protein levels and MMP-9 activity in fibroblasts, without significant changes in MMP-2 activity. MMP-9 activation by hypoxia requires LRP1 and Pyk2 phosphorylation in fibroblasts. Collectively, our in vivo and in vitro data support a major role of cardiac fibroblast LRP1 levels on MMP-9 up-regulation associated with ventricular remodelling after MI. |
Ayudas: | Instituto de Salud Carlos III FIS-PI14-01729 Instituto de Salud Carlos III FIS-PI14/01682 Ministerio de Ciencia e Innovación SAF2011-30067-C02-01 Agència de Gestió d'Ajuts Universitaris i de Recerca FI-DGR_B01008 Instituto de Salud Carlos III CD14/0109 |
Nota: | Altres ajuts: Fundació La Marató de TV3 (201521_10, 201502_30 and 080330), Red de Terapia Celular-TerCel (RD12/0019/0029), Red Cardio-vascular (RD12/0042/0027, RD12/0042/0047), Sociedad Española de Cardiología, Fundació Privada Daniel Bravo Andreu. |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | LRP1 ; MMP-9 ; Cardiac remodelling ; Myocardial infarction ; Ppyk2 |
Publicado en: | Journal of Cellular and Molecular Medicine, Vol. 21 (april 2017) , p. 1915-1928, ISSN 1582-4934 |
14 p, 3.8 MB |