Scavenger Receptor A1 Attenuates Aortic Dissection Via Promoting Efferocytosis In Mouse Macrophages

Macrophage class A1 scavenger receptor（SR-A1）is a pattern recognition receptor with an anti-inflammatory feature in cardiovascular diseases.However,its role in acute aortic dissection（AD）is not known yet.Using an aortic dissection model in SR-A1-deficient mice and their wild type littermates,we found that the loss of SR-A1 aggravated beta-aminopropionitrile monofumarate induced thoracic aortic dilation,false lumen formation,extracellular matrix degradation,vascular inflammation and accumulation of apoptotic cells.These pathological changes were associated with impaired macrophage efferocytosis mediated by tyrosine-protein kinase receptor Tyro3in vitro and in vivo.SR-A1 could directly interact with Tyro3 and was required for Tyro3 phosphorylation to activate its downstream PI3K/Akt signaling pathway.More importantly,co-culture of SR-A1^-/-macrophages with apoptotic Jurkat cells resulted in less devoured apoptotic cells accompanied by swelling mitochondria and damaged ATP generation,following poor IL-10 and robust TNF-αproduction.Nonetheless,deficiency of SR-A1 has no impact on phagolysosome formation during the efferocytosis.Lentiviral overexpression of Tyro3 or short-term exposure to agonist in SR-A1^-/-macrophages induced restorative phagocytosis in vitro.Furthermore,we found peritoneal macrophages from SR-A1^-/-mice exhibited restored efferocytosis when Tyro3 agonist Pros1 was administrated in vivo.These findings suggest that SR-A1-Tyro3 axis in macrophages mitigate AD damage by promoting efferocytosis and inhibiting inflammation.