Abstract 11457: Deficiency in Fractalkine Receptor Reduces Post-Infarction Cardiac Rupture by Preventing Down-Regulation of aE-catenin
Background: Fractalkine (FKN) promotes myocardial inflammation and fibrosis which are known to play crucial role in post-myocardial infarction (MI) cardiac rupture. Recent evidence showed that reduction in the expression and defective localization of αE-catenin was contributable to the patients dying of infarct rupture. However, it is completely unknown whether FKN has any influence on cardiac rupture. Here we used CX3CR1-/-(FKN receptor knockout) mice to investigate the hypothesis that FKN would predispose cardiac rupture by down-regulating αE-catenin.
Methods and Results: CX3CR1 wild type (WT) and knockout (KO) mice were subjected to the left coronary artery ligation to induce MI or sham operation. We found that myocardial FKN protein expression in response to 3 days ischemia was markedly increased. The incidence of cardiac rupture in 8 days after MI was significantly reduced in KO mice (14.3%) than in WT mice (41.7%) (p < 0.01). The infarct size in response to 24hrs ischemia in KO mice was markedly smaller than in WT-MI group. On day 3 after MI, the MMP-9 mRNA expression was increased by 6 folds in WT mice, while only 2 folds increase in KO mice. A similar change for myocardial myeloperoxidase (MPO) expression in response to 1 day ischemia was also found by immunohistochemistry, while the myocardial expression of αE-catenin protein on day 3 after infarction was significantly decreased in WT-MI mice, and it was only slightly reduced in KO-MI mice. In cultured neonatal rat cardiomyocytes, the αE-catenin expression was decreased significantly during anoxia with exposure to soluble FKN, which was blocked by Y27632, a ROCK1 inhibitor.
Conclusion: Fractalkine predisposes cardiac rupture by promoting myocardial inflammation and down-regulating αE-catenin through RhoA/ROCK1 pathway.
- © 2013 by American Heart Association, Inc.