Reparative myocardial mechanisms in adult C57BL/6 and MRL mice following injury

Physiol Genomics. 2007 Jun 19;30(1):44-52. doi: 10.1152/physiolgenomics.00070.2006. Epub 2007 Feb 27.

Abstract

Previous studies have suggested that the heart may be capable of limited repair and regeneration in response to a focal injury, while other studies indicate that the mammalian heart has no regenerative capacity. To further explore this issue, we performed a series of superficial and transmural myocardial injuries in C57BL/6 and MRL/MpJ adult mice. At defined time intervals following the respective injury (days 3, 14, 30 and 60), we examined cardiac function using echocardiography, morphology, fluorescence-activated cell sorting for 5-bromo-2-deoxyuridine-positive cells and molecular signature using microarray analysis. We observed restoration of myocardial function in the superficial MRL cryoinjured heart and significantly less collagen deposition compared with the injured hearts of C57BL/6 mice. Following a severe transmural myocardial injury, the MRL mouse has increased survival and decreased ventricular remodeling compared with the C57BL/6 mouse but without evidence of complete regeneration. The cytoprotective program observed in the severely injured MRL heart is in part due to increased cellular proliferation, increased vasculogenesis, and decreased apoptosis that limits the extension of the injury. We conclude that MRL injured hearts have evidence of myocardial regeneration, in response to superficial injury, but the stabilized left ventricular function and improved survival observed in the MRL mouse following severe injury is not associated with complete myocardial regeneration.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen / metabolism
  • Echocardiography
  • Flow Cytometry
  • Heart Injuries / etiology
  • Heart Injuries / genetics
  • Heart Injuries / physiopathology*
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism
  • Myosin Light Chains / genetics
  • Myosin Light Chains / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Regeneration / genetics
  • Regeneration / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription, Genetic
  • Ventricular Remodeling / genetics
  • Ventricular Remodeling / physiology
  • Wound Healing / genetics
  • Wound Healing / physiology
  • Wounds, Penetrating / complications

Substances

  • Myosin Light Chains
  • Collagen
  • Myosin Heavy Chains