Rebuilding a heart: complete regeneration after myocardial infarction in the axolotl (1151.1)

Abstract

Intro: Cardiac failure resulting from myocardial infarction is a leading cause of death. This is the fatal result of the lack of regenerative capacity of the mammalian heart. Salamanders such as the axolotl possess unmatched regenerative capacity, mastering the ability to regenerate internal organs and whole limbs. To draw basic information about molecular and cellular mechanisms in cardiac repair, we have established and validated a myocardial infarction model in the axolotl.M&M: Myocardial infarction in the axolotl was induced by cryoinjury. Regeneration was described histologically at 4, 7, 14, 31, 40 and 94 days post infarction (dpi) and 4 days post sham (dps). Concurrently functional restoration of cardiac output was monitored using echocardiography and MRI. Protein profiles of myocardial tissue 4, 14 and 30 dpi and 4 dps were produced using LC‐MS/MS.Results & Discussion: The axolotl restores complete myocardial structure and functionality within 2‐3 months after a 25% myocardial infarction. Interestingly, the initial response to injury is fibrosis forming a scar as found in mammals. However, this response is replaced within a few weeks when cardiomyocytes are deposited in the fibrotic scaffold aiding a gradual recovery of cardiac output.This model can potentially improve our understanding of heart regeneration, and we seek to identify signaling events at the protein level using the proteomics data.