Abstract 526: Activated Platelets And Osteopontin Contribute To Arterial Stiffness And Are Involved In Abdominal Aortic Aneurysm

Abstract

Significance: Chronic inflammation is a consistent theme in the progression of cardiovascular disease including AAA. Chronic inflammation contributes to aortic wall weakening in AAA by disrupting the ECM and promoting aortic stiffness. Various cell types (fibroblast, macrophages, VSMCs, and circulating platelets) and inflammatory signaling cascades are implicated in aortic wall weakening. Osteopontin (OPN) is a well-known pro-inflammatory cytokine, which is secreted by pro-inflammatory cells and has been found upregulated in AAA patients. However, its mechanistical pathway in disease’ progression and which cells participate in OPN signaling are unclear. Interestingly, literature suggests that activated platelets can drive OPN secretion in proximal inflammatory cells. Therefore, the aim of this project was to determine whether a mechanistic link exists among the activated platelets and OPN production in cells associated with AAA that eventually increases local aortic stiffness and promotes AAA progression. Methods: Human platelets were isolated from donor blood and activated to obtain activated platelet supernatants (APS). M1 macrophages (M1), adventitial fibroblasts (Fib) and vascular smooth-muscle cells (VSMC) were exposed to APS.Full-length OPN and its fragments, generated by thrombin, plasmin and MMP-2 and -9 cleavage, were incubated with the same cell populations as mentioned above. Stiffness-related gene expression and MMP-2 and -9 activity was investigated utilizing qRT-PCR and gelatin zymography, respectively. Results: On exposure to APS, stiffness related gene expression as well as MMPs activity was significantly altered in the vascular cell types. Downstream effects of OPN on aortic stiffness presented changes in OPN treated cells compared to control. Conclusion: Our results indicate that activated platelets contribute to aortic stiffness and induction of vascular inflammation by modulating OPN expression, suggesting a potential role in AAA pathobiology.