Lack of LRP8 triggers the formation of aortic dissection in angiotensin II infused mice - 06/01/20
Résumé |
Background |
Factor XI-thrombin amplification loop depends on platelets and monocytes and augments angiotensin II (AngII) driven vascular injury in experimental hypertension in mice. Low-density lipoprotein receptor-related protein 8 (LRP8) plays an important role in apolipoprotein E homeostasis and was also found to be important in endothelial barrier stabilization. Moreover, LRP8 is able to form a complex with the platelet glycoprotein Ib alpha (GPIbalpha) which is the main receptor for von Willebrand factor.
Purpose |
To explore the role of LRP8 and GPIbalpha in the development of hypertension related to platelet-dependent thrombin generation.
Methods |
We infused LRP8 KO mice with AngII for either 1 or 4 weeks using osmotic minipumps. Blood pressure was recorded using tail cuff measurement. Vascular reactivity was assessed in isolated aortic segments. Leukocyte activation and infiltration were assessed by flow cytometry of aortic tissue and intravital videomicroscopy imaging (IVM). Histology of aortas was performed with sirius red staining.
Results |
Infusion of AngII for 1 week in LRP8 KO mice altered endothelial dependent and independent vascular relaxation to the same extend as in control mice. Vascular rolling and adherence to the carotid endothelium, visualized by IVM was similar between LRP8 KO and control mice infused with AngII. There were no significant differences in AngII-induced blood pressure increase between the LRP8 KO and control mice. Unexpectedly, LRP8 KO mice demonstrated a drastically increased mortality rate in response to AngII infusion. In the 4 weeks AngII infusion experiments, 80% of the LRP8 KO mice died within the first 10 days of AngII infusion due to aortic dissection complicated by hemorrhage.
Conclusion |
LRP8 receptor dysfunction lead to the formation of aortic dissection in AngII infused mice. Further studies are needed to better characterize the role of immune cells and platelets in the development of these dissections.
Le texte complet de cet article est disponible en PDF.Plan
Vol 12 - N° 1
P. 134-135 - janvier 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.