Long Chain Omega-3 Polyunsaturated Fatty Acids Improve Vascular Stiffness in Abdominal Aortic Aneurysm: A Randomized Controlled Trial.

Abdominal aortic aneurysm (AAA) is a vascular disease involving permanent focal dilation of the abdominal aorta (≥30 mm) that can lead to catastrophic rupture. Destructive remodeling of aortic connective tissue in AAA contributes to wall stiffening, a mechanical parameter of the arterial system linked to a heightened risk of cardiovascular morbidity and mortality. Since aortic stiffening is associated with AAA progression, treatment options that target vascular inflammation would appear prudent. Given this, and growing evidence indicating robust anti-inflammatory and vasoprotective properties for long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), this study evaluated the impact of these nutrients (1.8 g/day for 12 weeks) on indices of vascular stiffness in patients with AAA. At baseline, pulse wave velocity (PWV) and augmentation index normalized to a heart rate of 75 bpm (AIx75) were significantly higher in patients with AAA compared to control participants (PWV: 14.2 ± 0.4 m.s-1 vs. 12.6 ± 0.4 m.s-1, p = 0.014; AIx75: 26.4 ± 1.7% vs. 17.3 ± 2.7%, p = 0.005). Twelve-week LC n-3 PUFA supplementation significantly decreased PWV (baseline: 14.2 ± 0.6 m.s-1, week 12: 12.8 ± 0.7 m.s-1, p = 0.014) and heart rate (baseline: 63 ± 3 bpm, week 12: 58 ± 3 bpm, p = 0.009) in patients with AAA. No change was observed for patients receiving placebo capsules. While this raises the possibility that LC n-3 PUFAs provide improvements in aortic stiffness in patients with AAA, the clinical implications remain to be fully elucidated.

Abdominal Aortic Aneurysm (AAA): Is There a Role for the Prevention and Therapy Using Antioxidants?

BACKGROUND: Abdominal aortic aneurysm (AAA) is a degenerative disease that causes mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seem to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin. OBJECTIVES: Human studies confirmed that oxidative stress and endothelial dysfunction, an important source of ROS production, were well associated with AAA development. Reducing oxidative stress by antioxidants can therefore be a good strategy for limiting AAA development. The objective of the present study is to review literature data favoring or not such a hypothesis. There is currently no evidence showing that strategies using classical low molecular weight antioxidants (vitamins C and E, ß- carotene) as target for ROS is effective to reduce human AAA progression. However, recent epidemiological data have highlighted the positive role of a diet enriched in fruits which contain high amounts of antioxidant polyphenols. By their ability to restore endothelial function and also their capacity to stimulate enzymatic antioxidants through activation of the Keap1/Nrf2/ARE pathway, polyphenols can represent a promising treatment target for reducing human AAA progression. CONCLUSION: Clinical studies are therefore urgently necessary to confirm the potential beneficial effect of polyphenols in preventing or limiting AAA.

Drug Therapy for Abdominal Aortic Aneurysms Utilizing Omega-3 Unsaturated Fatty Acids and Their Derivatives.

BACKGROUND: Abdominal aortic aneurysms (AAA) are life-threatening because of the potential for rupture, resulting in death. The current standard treatment for AAA is surgery, comprising laparotomic graft replacement and endovascular repair. However, because surgery carries the risk of major complications and re-intervention, drug therapies are desirable because they may reduce the occurrence of enlargement and rupture. OBJECTIVE: Recent research shows that the progression of AAA is related to inflammatory reactions, especially those in the NF-κB pathway. Omega-3 polyunsaturated fatty acids (PUFA) show antiinflammatory effects. Some derivatives of omega-3 PUFA are known as specialized pro-resolving lipid mediators (SPM) such as resolvins. They play an important role in resolving inflammation. CONCLUSION: Omega-3 PUFA and SPM may show promised effects for drug treatment of AAA.

Abdominal aortic aneurysm and omega-3 polyunsaturated fatty acids: Mechanisms, animal models, and potential treatment.

Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with macrophage accumulation in the adventitia, oxidative stress, medial elastin degradation and aortic dilation. Progression of AAA is linked to increased risk of rupture, which carries a high mortality rate. Drug therapies trialled to date lack efficacy and although aneurysm repair is available for patients with large aneurysm, peri-surgical morbidity and mortality have been widely reported. Recent studies using rodent models of AAA suggest that long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) and their metabolites can moderate inflammation and oxidative stress perpetuated by infiltrating macrophages and intervene in the destruction of medial elastin. This review examines evidence from these animal studies and related reports of inhibition of inflammation and arrest of aneurysm development following prophylactic supplementation with LC n-3 PUFAs. The efficacy of LC n-3 PUFAs for management of existing aneurysm is unclear and further investigations involving human clinical trials are warranted.

Comparison of Efficacy of Endovascular Aneurysm Repair Versus Open Surgical Repair in Middle/High-Risk Patients With Abdominal Aortic Aneurysm.

To explore the efficacy of endovascular aneurysm repair (EVAR) compared with traditional open surgical repair (OSR) in the treatment of middle/high-risk patients with abdominal aortic aneurysm (AAA). With a retrospective method, we analyzed the clinical data of 57 patients with middle/high-risk AAA admitted to Linyi People's Hospital Affiliated to Shandong University from January 2010 to January 2014. Twenty-eight of the 57 patients received EVAR and 29 others received OSR. Statistical analysis was conducted by the design of spreadsheet according to preoperative, intraoperative, perioperative, and postoperative follow-up relevant information. Our study showed that the difference in baseline characteristics of different therapies in middle/high-risk AAA patients was not statistically significant in preoperative period (P > 0.05). In intraoperative period, the efficacy of middle/high-risk AAA patients in EVAR group was significantly superior to OSR group in terms of blood loss, blood transfusion, and general anesthesia rate (all P < 0.01). In perioperative period, the ICU observation time and the average fasting time of middle/high-risk AAA patients in EVAR group were remarkably lower than OSR group (all P < 0.01), but the average hospital stay and the operation cost of middle/high-risk AAA patients in EVAR group were notably higher than OSR group. In postoperative follow-up period, OSR group was identified with a lower incidence of surgery-related complications than EVAR group (P < 0.05), but EVAR group was demonstrated with a higher survival rate than OSR group (P < 0.05); after 12 months of follow-up, SF-36 scale scores in OSR group were higher than EVAR group (P < 0.05). In conclusion, EVAR may have a better short-term effect, whereas OSR may have a better long-term effect in the treatment of middle/high-risk AAA patients.

Aortic iron overload with oxidative stress and inflammation in human and murine abdominal aortic aneurysm.

OBJECTIVE: Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models. APPROACH AND RESULTS: Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2'-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2'-deoxyguanosine expression area and macrophage infiltration area in human and murine AAA walls. We next investigated the effects of dietary iron restriction on AAA formation in mice. Iron restriction reduced the incidence of AAA formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine AAA walls, and transferrin receptor 1-positive area was similar to areas where iron accumulated and F4/80 were positive. CONCLUSIONS: Iron is involved in the pathophysiology of AAA formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for AAA progression.

ß-Carotene Attenuates Angiotensin II-Induced Aortic Aneurysm by Alleviating Macrophage Recruitment in Apoe(-/-) Mice.

Abdominal aortic aneurysm (AAA) is a common chronic degenerative disease characterized by progressive aortic dilation and rupture. The mechanisms underlying the role of α-tocopherol and ß-carotene on AAA have not been comprehensively assessed. We investigated if α-tocopherol and ß-carotene supplementation could attenuate AAA, and studied the underlying mechanisms utilized by the antioxidants to alleviate AAA. Four-months-old Apoe(-/-) mice were used in the induction of aneurysm by infusion of angiotensin II (Ang II), and were orally administered with α-tocopherol and ß-carotene enriched diet for 60 days. Significant increase of LDL, cholesterol, triglycerides and circulating inflammatory cells was observed in the Ang II-treated animals, and gene expression studies showed that ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9 and MMP-12 were upregulated in the aorta of aneurysm-induced mice. Extensive plaques, aneurysm and diffusion of inflammatory cells into the tunica intima were also noticed. The size of aorta was significantly (P = 0.0002) increased (2.24±0.20 mm) in the aneurysm-induced animals as compared to control mice (1.17±0.06 mm). Interestingly, ß-carotene dramatically controlled the diffusion of macrophages into the aortic tunica intima, and circulation. It also dissolved the formation of atheromatous plaque. Further, ß-carotene significantly decreased the aortic diameter (1.33±0.12 mm) in the aneurysm-induced mice (ß-carotene, P = 0.0002). It also downregulated ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9, MMP-12, PPAR-α and PPAR-γ following treatment. Hence, dietary supplementation of ß-carotene may have a protective function against Ang II-induced AAA by ameliorating macrophage recruitment in Apoe(-/-) mice.