title: Ilk conditional deletion in adult animals increases cyclic GMP-dependent vasorelaxation.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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 sGC-PKG expression in vivo.
authors.affiliation: Faculty of Medicine, Department of Physiology, University of Alcala, Alcalá de Henares, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Serrano
authors.forename: Sergio
authors.initials: S
authors.lastname: De Frutos
authors.forename: Mercedes
authors.initials: M
authors.lastname: Griera
authors.forename: Diana
authors.initials: D
authors.lastname: Medrano
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Puyol
authors.forename: Shoukat
authors.initials: S
authors.lastname: Dedhar
authors.forename: Maria Piedad
authors.initials: MP
authors.lastname: Ruiz-Torres
authors.forename: Diego
authors.initials: D
authors.lastname: Rodríguez-Puyol
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D062965:Cyclic GMP-Dependent Protein Kinase Type I / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D000099200:Scaffold Protein ILK
chemical_list: D006152:Cyclic GMP; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D006162:Guanylate Cyclase; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D017346:Protein Serine-Threonine Kinases; D018160:Receptors, Cytoplasmic and Nuclear; D000071756:Soluble Guanylyl Cyclase; D000099200:Scaffold Protein ILK; C016276:8-bromocyclic GMP
keywords: Cyclic-GMP; Integrin-linked kinase; Nitric oxide; Soluble guanylate cyclase; Vascular reactivity