Crosstalk of platelets with macrophages and fibroblasts aggravates inflammation, aortic wall stiffening and osteopontin release in abdominal aortic aneurysm

Abstract

Abdominal 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 of SPP1 (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, Mmp9 and Col1a1 in 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.

Crosstalk between thrombospondin-1 and CD36 modulates platelet–RBC interaction limiting thrombosis and abdominal aneurysm formation

“…To further investigate the impact of platelet–RBC interactions and the procoagulant activity of these cells, we analyzed platelet–RBC interactions and procoagulant activity in an experimental mouse model of AAA (the pancreatic porcine elastase [PPE] model) and in patients with AAA. We recently detected elevated platelet activation and platelet-mediated inflammation in mice and patients with AAA (26). Here, histological analysis at day 28 after elastase infusion revealed that platelets and RBCs had migrated into the abdominal aorta of PPE mice (Figure 6A).…”