ILK conditional deletion in adult animals increases cyclic GMP-dependent vasorelaxation
Integrin-linked kinase (ILK) regulates proliferation, differentiation, cell adhesion, and motility in many cell types and has been related to cancer progression, fibrosis, and vascular diseases. We designed the present study to directly explore the effect of ILK deletion on the regulation of vascula...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2013 |
| País: | España |
| Institución: | Universidad de Alcalá (UAH) |
| Repositorio: | e_Buah Biblioteca Digital Universidad de Alcalá |
| Idioma: | inglés |
| OAI Identifier: | oai:ebuah.uah.es:10017/60955 |
| Acceso en línea: | http://hdl.handle.net/10017/60955 https://dx.doi.org/10.1093/cvr/cvt131 |
| Access Level: | acceso abierto |
| Palabra clave: | Integrin-linked kinase Nitric oxide Vascular reactivity Cyclic-GMP Soluble guanylate cyclase Medicina Medicine |
| Sumario: | Integrin-linked kinase (ILK) regulates proliferation, differentiation, cell adhesion, and motility in many cell types and has been related to cancer progression, fibrosis, and vascular diseases. We designed the present study to directly explore the effect of ILK deletion on the regulation of vascular tone through the soluble guanylate cyclase (sGC) /protein kinase G (PKG) pathway in healthy adult mice. Experiments were carried out using a tamoxifen-inducible CRE-LOX system to conditionally delete the ILK gene in adult mice. Mice lacking ILK expression (cKO) presented increased vascular content and increased activity of sGC and PKG, resulting in a more intense vasodilatory response to a single dose of a nitric oxide (NO) donor [sodium nitroprusside (SNP)] or PKG agonist [8-bromoguanosine 3,5-cyclic monophosphate sodium salt (8-Br)]. Five minutes after SNP or 8-Br administration the reduction in the systolic arterial pressure was enhanced in cKO mice (SNP WT: 7.4 1.2 mmHG; SNP cKO: 14.0 2.5; 8-Br WT: 2.9 1.5 mmHG; 8-Br cKO: 10.0 3.4 mmHG). ILK deletion restored the vascular response to SNP after chronic oral nitrite administration. In addition, ILK deletion also increased hypotensive SNP effect in angiotensin II-treated animals, suggesting a role for ILK in basal and pathological states. Deletion of ILK in adult animals increased the vascular response to NO. These findings show, for the first time, a requirement for ILK in regulating sGCPKG expression in vivo. |
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