Abstract 331: BLT1 Contributes to the Frequency and Size of Abdominal Aortic Aneurysms in Mice
5-lipoxygenase and its product LTB4 are highly expressed in human vascular disease. LTB4 signals primarily through its high-affinity G protein-coupled receptor BLT1, which is expressed not only on leukocytes but also on smooth muscle cells. Recent studies demonstrated a greater than two-fold reduction in atherosclerotic lesion formation in Apoe−/− /Blt1−/− mice as compared to Apoe−/− controls. In light of the potential effects of BLT1 on multiple vessel wall cell types, here we tested the hypothesis that BLT1 is also necessary for aneurysm formation in a well-established murine model that creates suprarenal aneurysms without modulating blood pressure. Chow-fed Apoe−/− and Apoe−/− /Blt1−/− mice were treated with angiotensin II (angII, 1000 ng/min/kg) or vehicle control via Alzet osmotic pumps beginning at 20 weeks of age. After 4 weeks of infusion, mice were sacrificed for blood collection, and morphometric analyses were performed with IP Lab software by blinded observers. All mice had comparable cholesterol and triglyceride levels, thus excluding these confounding variables. We found a reduced rate of aneurysm formation in the angII-treated Apoe−/− /Blt1−/− mice as compared to the angII-treated Apoe−/− mice (39% vs 81%, n≥16, p=0.02). We also found concordant reductions in the maximum suprarenal/infrarenal diameter and total suprarenal/infrarenal area in the angII-treated Apoe−/− /Blt1−/− mice as compared to the Apoe−/− controls (Diameter ratio: 1.75 ± 0.22 vs 2.55 ± 0.23, n≥12, p=0.02; Area ratio: 4.27 ± 0.16 vs 5.67 ± 0.29, n≥12, p=0.0003). Thus, we have shown that BLT1 contributes to the frequency and size of abdominal aortic aneurysms in mice using multiple metrics. These findings are clinically relevant because small-molecule antagonists to BLT1 are under development and would target multiple vessel wall constituents relevant to several vascular pathologies.