Abstract 2041: Enhanced Platelet Reactivity In The Presence Of Abdominal Aortic Aneurysm: Unveiling Vascular Dynamics

Abstract

Introduction: Abdominal aortic aneurysms (AAA) are a pro-inflammatory disease that frequently feature a nonocclusive intraluminal thrombus (ILT) at the expansion site. Platelet abundance is notable at the luminal interface of an ILT, and recent investigations conducted by our lab and others elucidate the pivotal involvement of platelets activation and adhesion in the pathogenesis of AAA. While inflammation is recognized to affect platelet physiology, the impact of inflammation associated with AAA on the platelet phenotype remains unclear. Therefore, our objective was to elucidate the impact of AAA on platelet phenotype. Methods and Results: Male C57BL/6J mice underwent laparotomy and either a sterile solution of 10 mg/mL elastase solution (n =6) or heat inactivated (HI) elastase solution (n = 4), used as control, was applied to the infrarenal aorta. Weekly ultrasounds demonstrated that mice treated with elastase had significantly elevated aortic diameter and AAA incidence as compared to HI treated controls. Platelet counts and volumes were assessed weekly via a veterinary hematology analyzer. While there was no significant difference in mean platelet volume, platelet counts in AAA mice were on the lower end of the reference range, comparable to human AAA patients. At 4 weeks following laparotomy, platelets were isolated via terminal IVC blood collection, washed, and subjected to a dose response curve of both thrombin (protease-activated receptor agonist; 0.1 U/mL - 1 U/mL) and convulxin (glycoprotein VI agonist; 10 ng/mL - 100 ng/mL). Surface expression of P-selectin was the measured by flow cytometry. Platelets isolated from mice with aneurysms had greater surface P-selectin after agonist exposure compared to HI control platelets. Additionally, we reanalyzed published RNA sequencing data from control and AAA patient isolated platelets and found several upregulated platelet surface markers in AAA patients as compared to controls. Conclusions: Our data indicates that AAA influences platelet reactivity and modifies surface marker expression. While more work is needed to fully elucidate the underlying mechanisms, our data has significant implications for understanding how systemic inflammatory diseases like AAA affects platelets.