Cardiovascular research
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Cardiovascular research · Dec 2012
Moderate elevation of intracellular creatine by targeting the creatine transporter protects mice from acute myocardial infarction.
Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia and heart failure. However, testing this hypothesis has not been possible since oral creatine supplementation is ineffectual at elevating myocardial creatine levels. We therefore used mice overexpressing creatine transporter in the heart (CrT-OE) to test for the first time whether elevated creatine is beneficial in clinically relevant disease models of heart failure and ischaemia/reperfusion (I/R) injury. ⋯ Elevation of myocardial creatine by 20-100% reduced myocardial stunning and I/R injury via pleiotropic mechanisms, suggesting CrT activation as a novel, potentially translatable target for cardiac protection from ischaemia.
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Cardiovascular research · Dec 2012
The Ca(v)3.1 T-type calcium channel is required for neointimal formation in response to vascular injury in mice.
Restenosis is an undesirable consequence following percutaneous vascular interventions. However, the current strategy for preventing restenosis is inadequate. The aim of this study was to investigate the role of low-voltage gated T-type calcium channels in regulating vascular smooth muscle cell (VSMC) proliferation during neointimal formation. ⋯ Ca(v)3.1 is required for VSMC proliferation during neointimal formation, and blocking of Ca(v)3.1 may be beneficial for preventing restenosis.