Abstract 278: Protective Effects of Niacin in a Murine Model of Abdominal Aortic Aneurysms
Introduction. Abdominal aortic aneurysms (AAAs) are common among the aging population, yet there is no effective pharmacotherapy. Neutrophils play a key role in the pathogenesis of AAA, by triggering inflammation, oxidative stress, matrix degradation and smooth muscle cell (SMC) death. Niacin, a vitamin with beneficial cardiovascular effects, was shown previously to reduce vascular neutrophil infiltration, MPO accumulation, and HOCl-induced endothelial dysfunction in a rabbit perivascular injury model.
Hypothesis We hypothesized that niacin would have beneficial effects to prevent AAA in a mouse model.
Methods LDL null mice were infused with angiotensin II (1000 ng/kg/min) for 14 days to induce AAA with (n=27) or without (n=18) 0.3% supplemental niacin in the drinking water. One group (n=6) received the DP1 receptor antagonist, laropiprant, in addition to niacin. We also investigated the effects of niacin on MMP release in a human neutrophil cell line (HL-60) and on viability of a murine SMC line (MOVAS-1) challenged with 100μM H2O2.
Results Niacin decreased the rate of AAA formation as compared to untreated control mice, 26% vs. 83%, respectively. In mice that survived the complete 14 day treatment period and did not die due to a ruptured AAA, the mean suprarenal aorta diameters were 1.20 mm (SEM 0.09) in niacin treated mice vs. 1.68 mm (SEM 0.12) in the control group, representing a niacin treatment effect of a 29% diameter decrease (p<0.5). Laropiprant did not have an effect on AAA formation, however did increase the blood pressure moderately. In HL-60 cells stimulated with TNF-α, niacin (10mM) decreased MMP 9 activity by 88% but had no effect on cell viability. In MOVAS-1 cells exposed to hydrogen peroxide, 10mM niacin had a protective effect, reducing cell death at 12 hours (50% dead cells with niacin + H2O2 vs. 93% dead cells with hydrogen peroxide alone, p=0.02).
Conclusions We conclude that niacin decreases the incidence of AAA and demonstrates pleiotropic effects on neutrophils and SMCs that may underlie its already known beneficial lipid modifying mechanisms. These novel findings suggest that niacin might be a safe, effective and inexpensive medical therapy for AAA.
- © 2013 by American Heart Association, Inc.