Hypertension

Galectin-3 Regulates Smooth Muscle Contraction and Blood Pressure by Modulating Ca V 1.2 Channel Function

CirculationPublished Mechanistic study

Authors' conclusion

These results provide strong evidence that Gal-based CaV1.2 channel modulators are novel therapeutic pathways for normalizing BP.

Study context

Population
Transfected HEK 293 cells, isolated smooth muscle cells and arteries from smooth muscle-specific Gal-3 knockout mice and wild-type littermates, spontaneously hypertensive rats, and human patients
Comparison
iGal3BP vs amlodipine and losartan
Outcome
Molecular mechanisms by which Gal-3 binds to and elevates membrane insertion of CaV1.2 channels, and effect of iGal3BP on BP
Methodological detailsin vitro, ex vivo, in vivo
  • In vitro
  • Ex vivo
  • In vivo

Main finding

As reported in the abstract

Gal-3 modulation of CaV1.2 channel function and BP
  • Gal-3 identified as novel binding partner and positive modulator of CaV1.2 via binding to the intracellular II-III loop
  • Gal-3 increased total and surface expression, current density and open probability of CaV1.2 channels
  • CaV1.2 and Gal-3 upregulated in hypertensive rat aortas and human pulmonary arteries
  • Conditional deletion of Gal-3 in smooth muscle markedly lowered CaV1.2 protein and blood pressure (BP) in mice
  • iGal3BP significantly reduced BP in spontaneously hypertensive rats by decreasing CaV1.2 protein expression

Further findings

Repeated iGal3BP administration

Cumulative peptide accumulation in mesenteric arteries and sustained reduction in BP

iGal3BP plus Gal-1 mimetic peptide · within 4 hours; sustained for 35 days

Sustained BP lowering in hypertensive rats
35 days
SBP returned to normotensive levels within 4 hours
  • Negative modulatory Gal-1 mimetic peptide mimicking Gal-1–CaV1.2 interaction

Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.

Original publication

Galectin-3 Regulates Smooth Muscle Contraction and Blood Pressure by Modulating Ca V 1.2 Channel Function. Circulation. Published 15 June 2026. doi:10.1161/circulationaha.126.080022

Summarised from the published abstract; every number is checked against it

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