Lack of NPR-C may cause aortic tears from high salt by disrupting cell energy balance

Natriuretic peptide receptor C (NPR-C) was found to be downregulated in the aortas of acute thoracic aortic dissection (TAD) patients.

• Vascular smooth muscle cell-specific NPR-C knockout mice developed TAD when treated with angiotensin II and a high salt diet, indicating NPR-C's role in TAD pathogenesis.
• Loss of NPR-C function led to extracellular matrix degeneration, increased vascular smooth muscle cell apoptosis, and heightened inflammation.
• Mitochondrial fatty acid oxidation genes were significantly downregulated in the thoracic aortas of NPR-C knockout mice treated with angiotensin II and high salt diet.
• Knockdown of NPR-C activated the ERK1/2 pathway, reducing the expression and activity of peroxisome proliferator-activated receptor γ, which in turn inhibited the expression of HADHB, a key protein in fatty acid oxidation.
• NPR-C agonist treatment reduced TAD progression in a mouse model, suggesting a protective role for NPR-C against TAD.
• Activation of mitochondrial trifunctional protein by spermidine prevented TAD formation in NPR-C knockout mice under stress conditions.

Simplified