Fibrinogen may help preserve vascular smooth muscle contractility and limit progression through Bmal1 signaling.
Evidence
This mixed human-and-mouse study combined a population analysis of nonsurgically managed acute AD patients, aortic tissue observations, mouse fibrinogen knockdown, and exogenous fibrinogen supplementation experiments.
Caveat
The human evidence is associative, while the therapeutic claim rests mainly on mouse AD models and dosing conditions that may not translate directly to patients.
Simplified
(AD) is a life-threatening vascular disease with a high mortality rate. Surgery is essential in the acute phase but carries significant risks, whereas elective surgery during the chronic phase yields better outcomes. However, no pharmacological therapy has been proven effective in slowing AD progression. In our recent pilot clinical study, an association between higher plasma fibrinogen levels and improved clinical outcomes was observed in AD patients, suggesting a potential protective role of fibrinogen. However, direct evidence supporting this hypothesis is lacking. In this study, a population-based analysis of nonsurgically managed patients with acute AD revealed a distinct association: fibrinogen levels <2 g/L were significantly associated with increased mortality, whereas levels >4 g/L were significantly associated with reduced mortality. Notably, fibrinogen was undetectable in aortic samples from control individuals without AD but accumulated in the aortic media of both AD patients and model mice. Importantly, fibrinogen accumulation was more pronounced in mice with advanced but unruptured AD, suggesting its role in maintaining vascular stability. AAV8-mediated fibrinogen knockdown significantly exacerbated AD, whereas exogenous supplementation with fibrinogen alleviated AD in mice, as evidenced by changes in the survival rate, aortic dilation, AD incidence, elastic fiber degradation, and collagen accumulation. Mechanistically, fibrinogen inhibited Bmal1 signaling, preventing detrimental vascular smooth muscle cell (VSMC) phenotypic transformation and contractility impairment. Finally, exogenous supplementation with the optimal dose of fibrinogen mitigates the progression of AD in mice. This study identified fibrinogen as a key regulator of VSMC contractility and aortic structural integrity, highlighting its potential as a novel therapeutic target to delay AD progression and extend the window for elective surgery.
Key numbers
41.3%
In-hospital mortality rate
Among 310 patients with acute receiving conservative treatment.
<2 g/L vs. >4 g/L
Fibrinogen levels linked to mortality
Low fibrinogen levels are a risk factor for increased mortality in acute patients.
Full Text
We can’t show the full text here under this license.
