Abstract 20091: Platelets Play Positive and Negative Roles in Abdominal Aortic Aneurysm Formation and Rupture
Objective: It is estimated that >90% of abdominal aortic aneurysm (AAA) patients are on anti-platelet regiments without documented benefit or clinical evaluation. Therefore, we examined the effects of pharmaceutical blockade of platelet activation in either early or late-stage angiotensin II (AngII)-induced AAA formation in a mouse model.
Methods and Results: Temporal studies: Male Ldlr-/- mice (8 weeks) fed a saturated fat and cholesterol-enriched diet were infused with AngII (1,000 ng/kg/min) via mini-osmotic pumps for 1, 3, 5, 7, and 28 days. Utilizing in vivo platelet and macrophage labeling agents, it was determined that platelet accumulation (1 day) precedes macrophage accumulation (3 days) in the abdominal aorta. Further, platelet factor 4, a marker of platelet activation, increased time-dependently during the 28 day infusion. Early therapy during AAA formation: Aspirin (30 mg/L via drinking water [ASA]) or diet supplemented with the P2Y12 inhibitor clopidogrel (50 mg/kg/day [Plavix]) was administered to mice 1 week prior to and throughout infusion (n > 15 all groups). These treatments significantly increased rupture-induced death versus placebo groups (P < 0.05; [0% placebo vs. 58% Plavix] and [10% placebo vs. 64% ASA]). Interventional therapy after the formation of an AAA: Ldlr-/- mice were infused for 28 days and then stratified, based on aortic lumen diameters, utilizing noninvasive ultrasonography into 4 different groups: ASA (30 mg/L via drinking water), ASA placebo control, Plavix (50 mg/kg/day via food), and Plavix placebo control. Mice were continuously infused with AngII for an additional 42 days. All treatments significantly decreased rupture-induced death versus placebo groups (P < 0.05; [66% placebo vs. 8% ASA] and [58% placebo vs. 0% Plavix]. In vivo imaging demonstrated these anti-platelet agents reduced abdominal macrophage infiltration and matrix metalloproteinase activity in the aorta.
Conclusion: We demonstrated platelets accumulate rapidly at the site of AAA formation and platelets are activated. Platelets provide hemostatic protection during AAA formation but appear to be pro-inflammatory once the AAA has formed. Our study suggests that anti-platelet therapy may reduce AAA rupture.
Author Disclosures: A. Owens III: None. Y. Boulaftali: None. W. Bergmeier: None. N. Mackman: None.
- © 2014 by American Heart Association, Inc.