Preclinical (mouse model) · PMID 41955717

Kisspeptin-10 attenuates pulmonary arterial hypertension via restoration of mitochondrial function in pulmonary artery smooth muscle cells — VialBase Research

KP-10 attenuates PAH via GPR54 receptor in SU5416/hypoxia mouse model

Last updated · 2026 · Huang S, Chen Z, Gong W, Song Y, Ding W, Zhang L, Li J · Neuropeptides
Key findings
  • KP-10 attenuates PAH via GPR54 receptor in SU5416/hypoxia mouse model
  • Reduced right ventricular systolic pressure, hypertrophy, and vascular remodeling
  • Restored mitochondrial membrane potential, ATP production, cytochrome c oxidase activity
  • Normalized PINK1/Parkin/FUNDC1 mitophagy protein accumulation
  • Inhibited hypoxia-induced PASMC proliferation in vitro
  • Identifies Kisspeptin/GPR54 axis as potential PAH therapeutic target

PMID 41955717 — Kisspeptin-10 in Pulmonary Arterial Hypertension

Compound: Kisspeptin Citation: Huang S et al. Neuropeptides. 2026;117:102611. doi:10.1016/j.npep.2026.102611

Summary

Demonstrates that Kisspeptin-10, acting via GPR54, attenuates pulmonary arterial hypertension (PAH) in a mouse model by restoring mitochondrial function in pulmonary artery smooth muscle cells (PASMCs).

Key Findings

  • In vivo: KP-10 reduced right ventricular systolic pressure, RV hypertrophy, and pulmonary vascular remodeling in SU5416/hypoxia PAH model
  • Mitochondrial restoration: Restored membrane potential, ATP production, and cytochrome c oxidase activity in hypoxic PASMCs and PAH lungs
  • Mitophagy normalization: Reduced excessive accumulation of PINK1, Parkin, and FUNDC1 proteins
  • Anti-proliferative: Directly inhibited hypoxia-induced PASMC proliferation in vitro

Significance

Reveals a non-reproductive function of kisspeptin — mitochondrial protection in cardiovascular disease. The GPR54 axis represents a novel therapeutic target for PAH, expanding kisspeptin’s potential beyond reproductive endocrinology. Parallels with SS-31‘s mitochondrial mechanisms are notable.

PubMed

See Also