NAMPT modulates muscle fiber type transition in PAD myopathy via the cGMP-PKG signaling pathway

Peripheral artery disease (PAD), caused by atherosclerosis resulting in reduced blood flow in the lower extremities, impairs both skeletal muscle mass and function in humans, and its molecular mechanism is not clear. Recent studies have demonstrated that Nicotinamide phosphoribosyl transferase (NAMPT) influences skeletal muscle mass and function by modulating NAD⁺ levels and cellular Ca²⁺ homeostasis. However, its role in muscle fiber type transition remains to be elucidated.

NAMPT is downregulated in ischemic skeletal muscle and CoCl₂-treated C2C12 myotubes. NAMPT enhances the functional performance of ischemic limbs, reduces apoptosis, increases the formation of oxidative muscle fibers, and improves mitochondrial function. The cGMP‒PKG pathway is activated by NAMPT in ischemic limbs. Exogenous inhibition of cGMP-PKG signaling inhibits the formation of oxidative muscle fibers induced by NAMPT.

NAMPT protects against ischemic limb injury via the cGMP‒PKG signaling pathway, suggesting that it is a promising therapeutic and predictive target for myopathy associated with PAD.

Not applicable.