Scavenger receptor A1 attenuates aortic dissection via promoting efferocytosis in macrophages

Biochemical Pharmacology
Zhi ZhangQi Chen

Abstract

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 SR-A1 deficiency 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 an impaired macrophage efferocytosis mediated by tyrosine-protein kinase receptor Tyro3 in 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. 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-α production. Deficiency of SR-A1 did not influence phagolysosome formation during the efferocytosis. Lentiviral overexpression of Tyro3 in SR-A1-/- macrophages induced restorative phagocytosis in vitr...Continue Reading

Citations

Mar 3, 2020·Frontiers in Physiology·Xinhao WangWei Guo
Dec 5, 2019·Frontiers in Immunology·Andrea Kristina HorstLinda Diehl
May 14, 2020·International Journal of Molecular Sciences·Makiko Hayashi-HoriYoshihiro Fukumoto
Aug 10, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xianfeng LiuXianli Meng

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