Inherent Metabolic Adaptations in Adult Spiny Mouse ( Acomys ) Cardiomyocytes Facilitate Enhanced Cardiac Recovery...

Area of Science:

• Cardiovascular Biology
• Metabolic Regulation
• Mammalian Heart Regeneration

Background:

• Adult mammalian hearts have limited regenerative capacity post-injury, often leading to heart failure.
• The spiny mouse (Acomys) exhibits unique cardiac ischemic resilience, unlike standard laboratory mice (Mus musculus).
• Mechanisms underlying Acomys' enhanced recovery after myocardial infarction (MI) are not well understood.

Approach:

• Single-nucleus RNA sequencing (snRNA-seq) was used to analyze cardiomyocyte transcriptomic profiles in Acomys and Mus at baseline and post-MI.
• Targeted metabolomics, stable isotope-resolved metabolomics, and functional mitochondrial assays were performed on heart tissues.
• These multi-omics approaches elucidated metabolic adaptations in cardiomyocytes following ischemic injury in both species.

Key Points:

• Acomys cardiomyocytes inherently upregulate glycolysis, pentose phosphate pathway, and glutathione metabolism, while downregulating oxidative phosphorylation (OXPHOS).
• This metabolic profile in Acomys is associated with reduced reactive oxygen species (ROS) production and increased antioxidant capacity.
• Stable isotope tracing and functional assays confirmed Acomys' reliance on glycolysis and adaptive metabolic flexibility post-MI.

Conclusions:

• Unique metabolic characteristics of Acomys cardiomyocytes contribute to their superior ischemic resilience and cardiac repair post-MI.
• Metabolic flexibility plays a crucial role in determining cardiomyocyte response to ischemic injury in adult mammals.
• Acomys serves as a valuable model for investigating cardiac ischemic resilience and potential therapeutic strategies.