Fibrinogen-Bmal1 signaling as a therapeutic target to limit aortic dissection by preserving VSMC contractility - PubMed
2 hours ago
- #aortic dissection
- #fibrinogen
- #VSMC contractility
- Aortic dissection (AD) is a life-threatening vascular disease with high mortality, and current surgical treatments carry significant risks.
- Higher plasma fibrinogen levels are associated with improved clinical outcomes in AD patients, suggesting a protective role.
- Fibrinogen levels <2 g/L increase mortality, while levels >4 g/L reduce mortality in nonsurgically managed AD patients.
- Fibrinogen accumulates in the aortic media of AD patients and model mice, especially in advanced but unruptured cases.
- AAV8-mediated fibrinogen knockdown worsens AD, while exogenous fibrinogen supplementation alleviates AD symptoms in mice.
- Fibrinogen inhibits Bmal1 signaling, preventing detrimental vascular smooth muscle cell (VSMC) transformation and contractility impairment.
- Exogenous fibrinogen supplementation at optimal doses can mitigate AD progression, highlighting its potential as a therapeutic target.