Dynamic Obstruction is Associated With Abnormal Myocardial Mechanics in Hypertrophic Cardiomyopathy

Introduction: Dilated cardiomyopathy (DCM) is a progressive disease characterised by ventricular dilatation, impaired systolic function and diffuse interstitial fibrosis. Recently in the setting of mineralocorticoid-induced cardiac fibrosis, we demonstrated that activation of the SDF-1:CXCR4 axis was central to the development of cardiac fibrosis. In this study we tested the hypothesis that the SDF-1:CXCR4 axis is implicated in the pathogenesis of fibrosis in DCM. Methods and results: A transgenic mouse model (Mst1) of DCM and fibrosis was used. The effect of the CXCR4 antagonist (AMD3100, 6mg/kg/d) on cardiac fibrosis (quantitative Masson’s stain) was examined. After 12wks, blood pressure and left ventricular morphology was analysed. As indicated in the Table, Mst1 mice demonstrated ventricular dilatation and significant cardiac fibrosis. AMD3100 significantly attenuated the development of left ventricular fibrosis (p< 0.01). Conclusion: CXCR4/SDF-1 signalling pathway plays a central role in thepathogenesis of cardiac fibrosis inDCM.