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Smooth Muscle lncRNA CARMN Identified as Therapeutic Target for Chronic Limb Ischemia

Preclinical work shows HHIP inhibition or microRNA-143-3p overexpression restores perfusion in ischemic mouse limbs.

Overview

  • Researchers profiled human skeletal muscle from chronic limb‑threatening ischemia patients and mouse limb‑ischemia models and pinpointed the long non‑coding RNA CARMN as reduced in disease tissue.
  • CARMN is expressed in vascular smooth muscle cells rather than endothelial cells, shifting attention away from long‑studied endothelial growth factors that have failed in clinical trials.
  • Genetic deletion of CARMN in mice produced poor blood‑flow recovery, reduced capillary density, limb tissue necrosis, and amputation‑like outcomes.
  • Mechanistic experiments mapped a miR‑143‑3p–HHIP signaling axis controlled by CARMN that links smooth muscle signaling to endothelial angiogenesis and tissue repair.
  • Blocking HHIP or elevating its regulating microRNA fully rescued angiogenesis, perfusion, and healing in models, and investigators are now probing upstream regulators that lower CARMN during ischemia.