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J Cell Physiol. 2014 Jul;229(7):845-55. doi: 10.1002/jcp.24511.

Acetylsalicylic acid inhibits IL-18-induced cardiac fibroblast migration through the induction of RECK.

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1
Research Service, Southeast Louisiana Veterans Health Care System, New Orleans, Louisiana; Heart and Vascular Institute, Tulane University School of Medicine, New Orleans, Louisiana.

Abstract

The pathogenesis of cardiac fibrosis and adverse remodeling is thought to involve the ROS-dependent induction of inflammatory cytokines and matrix metalloproteinases (MMPs), and the activation and migration of cardiac fibroblasts (CF). Here we investigated the role of RECK (reversion-inducing-cysteine-rich protein with Kazal motifs), a unique membrane-anchored MMP regulator, on IL-18-induced CF migration, and the effect of acetylsalicylic acid (ASA) on this response. In a Matrigel invasion assay, IL-18-induced migration of primary mouse CF was dependent on both IKK/NF-κB- and JNK/AP-1-mediated MMP9 induction and Sp1-mediated RECK suppression, mechanisms that required Nox4-dependent H(2)O(2) generation. Notably, forced expression of RECK attenuated IL-18-induced MMP9 activation and CF migration. Further, therapeutic concentrations of ASA inhibited IL-18-induced H(2)O(2) generation, MMP9 activation, RECK suppression, and CF migration. The salicylic acid moiety of ASA similarly attenuated IL-18-induced CF migration. Thus, ASA may exert potential beneficial effect in cardiac fibrosis through multiple protective mechanisms.

PMID:
24265116
PMCID:
PMC4408083
DOI:
10.1002/jcp.24511
[Indexed for MEDLINE]
Free PMC Article
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