Altered trace elements and ascorbic acid metabolism have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, their role in the disease process, or the effect of atherosclerosis on their tissue levels within plaque, is poorly understood. The present study analyzes the concentrations of Fe, Cu, Zn, and Mn, and ascorbic acid and superoxide dismutase (SOD) activity in tissue samples from 29 patients with abdominal aortic aneurysms (AAA) and 14 patients with atherosclerotic occlusive disease (AOD). It was observed that the Fe and Mn concentrations in AAA and AOD tissue were higher than the levels in nondiseased control aorta, whereas Cu and Zn levels in AAA and AOD tissue were similar to the levels in controls. The Zn:Cu ratio was significantly lower in the AAA tissue in comparison to both AOD and control tissue. In addition, AAA and AOD tissue had low ascorbic acid levels and low Cu,Zn-SOD activity with Cu,Zn-SOD:Mn-SOD ratios of 0.27 and 0.19, respectively, compared to a ratio of 3.20 in control aorta. These data indicate that aorta affected by aneurysms and occlusive disease have altered trace element and ascorbic acid concentrations, as well as low Cu,Zn-SOD activity. Although these observations do not directly support the hypothesis that AAA is associated with aortic Cu deficiency they do suggest a role for oxygen radicals or increased lipid peroxidation in occlusive and aneurysmal disease of the aorta.

The biochemical mechanisms by which hypertension accelerates atherosclerosis and increases the risk of aortic aneurysm rupture are poorly understood. This study evaluates the effects of hypertension on aortic trace element concentrations and antioxidant status in tissue removed from 26 normotensive (NT) and 20 hypertensive (HT) patients. Twenty-seven of 46 patients (59%) had aneurysmal (AA), and 19 of 46 (41%) had occlusive disease (OD). Aortic iron concentrations were markedly higher in both OD and AA tissue compared with controls. A similar trend was observed with copper concentrations, with the highest elevations observed in HT AA tissues. No significant differences were observed in zinc concentrations, except that HT AA aorta had significantly lower zinc levels than either OD or control tissue. Aortic ascorbic acid concentrations in diseased aorta were lower than those of controls, but independent of blood pressure. Copper-zinc-superoxide dismutase activity was similarly reduced, with the lowest activity observed in diseased aorta from HT patients. Only HT AA aorta had significantly higher manganese-superoxide dismutase activity than controls. The aortas of patients with AA had significantly lower amounts of elastin and greater elastase activity than either controls or those with OD. However, the differences were independent of blood pressure. Hypertensive patients with OD and AA had 31% more and 27% less aortic collagen, respectively, than their NT counterparts (P less than 0.05). These data suggest that the reduction in aortic collagen and elastin in HT patients with AA compared with their NT counterparts may explain the larger size of aneurysms and predispose to their eventual rupture. Furthermore, the diminished antioxidant status associated with HT predisposes to lipid peroxidation, which contributes to the acceleration of these processes. Our studies were conducted in patients with established aortic aneurysmal and occlusive disease. Whether these observations are pertinent to the pathogenesis of AA and OD remains unclear and merits further study.

BACKGROUND:Pathogenic immune responses are known to play an important role in abdominal aortic aneurysm (AAA) development. Ultraviolet B (UVB) irradiation has been demonstrated to have therapeutic potential not only for cutaneous diseases but also for systemic inflammatory diseases in mice by suppressing immunoinflammatory responses. We investigated the effect of UVB irradiation on experimental AAA.

METHODS AND RESULTS:We used an angiotensin II-induced AAA model in apolipoprotein E-deficient mice fed a high-cholesterol diet. Mice aged 10 weeks were irradiated with 5 kJ/mUVB once weekly for 6 weeks (UVB-irradiated, n=38; nonirradiated, n=42) and were euthanized for evaluation of AAA formation at 16 weeks. Overall, 93% of angiotensin II-infused mice developed AAA, with 60% mortality possibly because of aneurysm rupture. UVB irradiation significantly decreased the incidence (66%) and mortality (29%) of AAA (=0.004 and=0.006, respectively). UVB-irradiated mice had significantly smaller diameter AAA (=0.008) and fewer inflammatory cells in the aortic aneurysm tissue than nonirradiated mice, along with systemic expansion of CD4Foxp3regulatory T cells and decreased effector CD4CD44CD62LT cells in para-aortic lymph nodes. Genetic depletion of regulatory T cells abrogated these beneficial effects of UVB treatment, demonstrating a critical role of regulatory T cells.

CONCLUSIONS:Our data suggest that UVB-dependent expansion of regulatory T cells has beneficial effects on experimental AAA and may provide a novel strategy for the treatment of AAA.