Simvastatin blocks soluble SSAO/VAP-1 release in experimental models of cerebral ischemia: Possible benefits for stroke-induced inflammation control

Ping Sun, Mar Hernandez-Guillamón, Mireia Campos-Martorell, Alba Simats, Joan Montaner, Mercedes Unzeta, Montse Solé

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

© 2017 Elsevier B.V. Beyond cholesterol reduction, statins mediate their beneficial effects on stroke patients through pleiotropic actions. They have shown anti-inflammatory properties by a number of different mechanisms, including the inhibition of NF-κB transcriptional activity and the consequent increase and release of adhesion molecules. We have studied simvastatin's effects on the vascular enzyme semicarbazide-sensitive amine oxidase/vascular adhesion protein 1 (SSAO/VAP-1), which is involved in stroke-mediated brain injury. SSAO/VAP-1 has leukocyte-binding capacity and mediates the expression of other adhesion proteins through signaling molecules generated by its catalytic activity. Our results indicate that soluble SSAO/VAP-1 is released into the bloodstream after an ischemic stimulus, in parallel with an increase in E-selectin and VCAM-1 and correlating with infarct volume. Simvastatin blocks soluble SSAO/VAP-1 release and prevents E-selectin and VCAM-1 overexpression as well. Simvastatin also effectively blocks SSAO/VAP-1-mediated leukocyte adhesion, although it is not an enzymatic inhibitor of SSAO in vitro. In addition, simvastatin-induced changes in adhesion molecules are greater in human brain endothelial cell cultures expressing SSAO/VAP-1, compared to those not expressing it, indicating some synergic effect with SSAO/VAP-1. We think that part of the beneficial effect of simvastatin in stroke is mediated by the attenuation of the SSAO/VAP-1-dependent inflammatory response.
Original languageEnglish
Pages (from-to)542-553
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1864
Issue number2
DOIs
Publication statusPublished - 1 Feb 2018

Keywords

  • Brain ischemia
  • Endothelium
  • Inflammation
  • SSAO/VAP-1
  • Simvastatin

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