Dietary supplementation with omega-3 polyunsaturated fatty acids modulate matrix metalloproteinase immunoreactivity in a mouse model of pre-abdominal aortic aneurysm.

BACKGROUND: Two-day infusion of angiotensin II to apolipoprotein E-deficient (ApoE(-/-)) mice provides a model of pre-abdominal aortic aneurysm. Long chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory effects. This study examined the effect of an eight-week low or high n-3 PUFA diet in ApoE(-/-) mice on matrix metalloproteinase (MMP) expression and elastin degradation. METHODS: ApoE(-/-) mice were fed a low or high n-3 PUFA diet for eight weeks prior to two-day infusion with angiotensin II. The omega-3 index, MMP-2, MMP-9, TIMP-1, and TGF-ß1 immunoreactivity, and elastin fragmentation were measured. RESULTS: The omega-3 index with the low and high n-3 PUFA diet was 3.78% and 13.03%, respectively. MMP-9 immunoreactive stain intensity was lower in mice fed the high, compared to the low n-3 PUFA diet in endothelial cells (suprarenal aorta), and inflammatory cells (suprarenal and infrarenal aorta). Inflammatory cells had higher TIMP-1 and TGF-ß1 stain intensity in mice fed the high, compared to the low n-3 PUFA diet (suprarenal aorta). MMP-2 immunoreactivity was unaffected by diet. A non-significant trend for reduced elastin fragmentation was observed in mice fed the high n-3 PUFA diet. CONCLUSION: Dietary supplementation with n-3 PUFAs may have protective anti-inflammatory effects mediated through modulation of MMPs and TIMPs.

N-3 PUFAs protect against aortic inflammation and oxidative stress in angiotensin II-infused apolipoprotein E-/- mice.

Abdominal aortic aneurysm is associated with infiltration of inflammatory cells into the aortic wall. The inflammatory response is also evident in animal models, such as apolipoprotein E-deficient (ApoE-/-) mice that have been infused with angiotensin II, prior to development of aortic aneurysm. Since omega-3 polyunsaturated fatty acids (n-3 PUFAs) and their metabolites have anti-inflammatory and pro-resolving activity, we hypothesised that dietary supplementation with n-3 PUFAs would protect against inflammatory processes in this mouse model. Twenty C57 and 20 ApoE-/- 3-4 week old male mice were supplemented with a low (0.14%, n = 10/group) or high (0.70%, n = 10/group) n-3 PUFA diet for 8 weeks before 2-day infusion with 0.9% saline or angiotensin II (1000 ng/kg/min). Four ApoE-/- mice on the low n-3 PUFA diet and none of the ApoE-/- mice on the high n-3 PUFA diet showed morphological evidence of abdominal aortic dissection. The plasma concentration of the n-3 PUFA metabolite, resolvin D1 was higher in angiotensin II-infused ApoE-/- mice fed the high, compared to the low n-3 PUFA diet. The number of neutrophils and macrophages infiltrating the abdominal aorta was elevated in ApoE-/- mice on the low n-3 PUFA diet, and this was significantly attenuated in mice that were fed the high n-3 PUFA diet. Most neutrophils and macrophages were associated with dissected aortas. Immunoreactivity of the catalytic subunit of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, Nox2, and superoxide were elevated in ApoE-/- mice that were fed the low n-3 PUFA diet, and this was also significantly attenuated in mice that were fed the high n-3 PUFA diet. Together, the findings indicate that supplementation of ApoE-/- mice with a diet high in n-3 PUFA content protected the mice against pro-inflammatory and oxidative stress responses following short-term infusion with angiotensin II.