Abstract 8096: Transplantation of Mesenchymal Stem Cells Alters Ion Channel Gene Expression and Mitigates Cardiac Electrophysiological Remodelling in a Rat Model of Myocardial Infarction
The aim of this study was to evaluate the impacts of mesenchymal stem cell (MSC) transplantation on electrophysiological remodelling following myocardial infarction (MI).
Methods: Three weeks after coronary ligation, 3×106 MSCs, or culture medium alone, were directly injected into infarcted Lewis rat hearts. Hearts were excised one to two weeks later, Langendorff-perfused, optically mapped using the potentiometric dye di-4-ANEPPS, and then fixed and sectioned for morphometric and histological analyses. Gene expression was assessed by qRT-PCR.
Results: Optical mapping showed that MSC transplantation attenuated the reduction in conduction velocity (CV) and the prolongation of effective refractory period (ERP) in infarcted hearts. These electrophysiological changes correlated with higher vascular density and better-preserved ventricular wall thickness in MSC-treated hearts. A number of ion channel genes showed post-MI changes in expression. In particular, the expression of Kir2.1, which mediates the inward rectifier K+ current IK1, was reduced in MI and partially restored with MSC transplantation.
Conclusion: Apart from well-documented benefits such as promoting angiogenesis and limiting adverse structural remodelling, MSC transplantation improves conduction and reduces refractoriness in infarcted hearts. MSCs also partially restore Kir2.1 expression, which would enhance IK1 and contribute to a more negative resting membrane potential, allowing for more Na+ channels to open during depolarization and improving CV. As IK1 contributes to repolarization, restoring Kir2.1 expression would also attenuate ERP prolongation. Our experiments showed that MSCs have the capacity to alter cardiac ion channel expression and mitigate adverse electrophysiological remodelling following MI. Thus MSC transplantation may be a potential strategy to prevent post-MI arrhythmias.
- © 2011 by American Heart Association, Inc.