Tirzepatide reduces lung blood vessel changes in pulmonary arterial hypertension linked to the SIRT1/H4K12la/c-Jun pathway

Tirzepatide significantly improves echocardiographic indicators of pulmonary vascular load in pulmonary arterial hypertension.

• Metabolic reprogramming and phenotypic switching in pulmonary arterial smooth muscle cells are key features of pulmonary arterial hypertension.
• Tirzepatide suppresses the phenotypic switching of these cells, potentially reducing vascular remodeling.
• The medication corrects the Warburg effect, decreasing intracellular lactate levels associated with the synthetic phenotype in these cells.
• Activation of the AMPK/SIRT1 signaling pathway by Tirzepatide leads to a notable reduction in a specific epigenetic modification (H4K12la).
• This reduction suppresses the transcription of the proto-oncogene Jun, which is linked to the worsening of pulmonary arterial hypertension.

Simplified