Platelets modulate inflammation and matrix remodeling in abdominal aortic aneurysm

Abstract

AbstractAbdominal aortic aneurysm (AAA) is a highly lethal disease with progressive dilatation of the abdominal aorta accompanied by degradation and remodelling of the vessel wall due to chronic inflammation. Platelets are small anuclear cells that can release various inflammatory cytokines and biological response modulators when activated. In cardiovascular diseases, platelets are crucial for the inflammatory response but their role in AAA is poorly understood. However, both -experimental and clinical data-strongly suggest that platelet activation may be relevant for AAA formation and progression. Here, we find that platelets play a crucial role in promoting AAA through modulation of inflammation and degradation of the ECM. They are responsible for the up-regulation ofSPP1(osteopontin, OPN) gene expression in macrophages and aortic tissue, which triggers inflammation and remodeling. Further, enhanced platelet activation and pro-coagulant activity results in elevated gene expression of various cytokines,Mmp9andCol1a1in macrophages. Platelet depletion in experimental murine AAA reduced inflammation and ECM remodeling, with reduced elastin fragmentation and aortic diameter expansion. In conclusion, our data strongly supports the potential relevance of anti-platelet therapy to reduce AAA progression and rupture in AAA patients.