Targeting protein tyrosine phosphatase σ after myocardial infarction restores cardiac sympathetic innervation and prevents arrhythmias
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- Targeting protein tyrosine phosphatase σ after myocardial infarction restores cardiac sympathetic innervation and prevents arrhythmias
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Millions of people suffer a myocardial infarction (MI) every year, and those who survive have increased risk of arrhythmias and sudden cardiac death. Recent clinical studies have identified sympathetic denervation as a predictor of increased arrhythmia susceptibility. Chondroitin sulfate proteoglycans present in the cardiac scar after MI prevent sympathetic reinnervation by binding the neuronal protein tyrosine phosphatase receptor σ (PTPσ). Here we show that the absence of PTPσ, or pharmacologic modulation of PTPσ by the novel intracellular sigma peptide (ISP) beginning 3 days after injury, restores sympathetic innervation to the scar and markedly reduces arrhythmia susceptibility. Using optical mapping we observe increased dispersion of action potential duration, supersensitivity to β-adrenergic receptor stimulation and Ca(2+) mishandling following MI. Sympathetic reinnervation prevents these changes and renders hearts remarkably resistant to induced arrhythmias.
Original language | English |
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Article number | 6235 |
Journal | Nature Communications |
Volume | 6 |
Number of pages | 9 |
ISSN | 2041-1723 |
DOIs | |
Publication status | Published - 2 Feb 2015 |
Externally published | Yes |
- Animals, Arrhythmias, Cardiac/prevention & control, Calcium/metabolism, Electrocardiography, Female, Male, Mice, Mice, Inbred BALB C, Mice, Transgenic, Myocardial Infarction/drug therapy, Peptides/therapeutic use, Receptor-Like Protein Tyrosine Phosphatases, Class 2/antagonists & inhibitors, Receptors, Adrenergic, beta/metabolism, Sympathetic Nervous System/metabolism
Research areas
ID: 248114734