Is aortic aneurysm preventable?

Abstract

Abdominal aortic aneurysm (AAA) is a chronic inflammatory condition, triggered by the local accumulation of macrophages, oxidative stress and damage to the aortic wall. Pro-inflammatory eicosanoids seem to play a significant role in AAA. The pro-inflammatory events seen in AAA could be due to a deficiency of anti-inflammatory eicosanoids such as lipoxin A4 (LXA4), resolvins, protectins and maresins as a result of reduced tissue concentrations of their precursors: arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Thus, an imbalance between pro- and anti-inflammatory eicosanoids may underlie AAA. Angiotensin-II (Ang-II), a pro-inflammatory molecule, seems to have a role in AAA. I propose that AAA is due to the local (abdominal aortic wall) deficiency of AA and other PUFAs and their anti-inflammatory metabolites especially LXA4. The beneficial action of EPA and DHA reported in the animal experimental models of AAA induced by Ang-II infusion can be attributed to their (EPA and DHA) ability to enhance the formation of not only resolvins, protectins and maresins but also LXA4. It is likely that abdominal aortic tissue (endothelial cells, smooth muscle cells and other cells) may be deficient in AA, EPA and DHA, and have defective activity of 5-, 12-, and 15-lipoxygenases and cyclooxygenase, especially COX-2 resulting in decreased formation of LXA4, resolvins, protectins and maresins. Thus, methods designed to enhance the formation of LXA4 and other anti-inflammatory eicosanoids may form a new approach to prevent and manage AAA.

Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1α/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm

“…Many previous studies have also documented the inhibitory effects of quercetin on cyclooxygenase-2 (COX-2) expression [ 18 ] and angiogenesis [ 19 ]. Moreover, the AAA development has been characterized by the increased expression of COX-2, and the inactivation of COX-2 may lead to a new approach to prevent AAA expansion [ 20 – 22 ]. It is worth mentioning that rigorous analyses reveal that COX-2 upregulation is transcriptional and is associated with the hypoxia-inducible factor 1 α (HIF-1 α ) induction [ 23 ].…”

Transcription factor TCF3 promotes macrophage-mediated inflammation and MMPs secretion in abdominal aortic aneurysm by regulating miR-143-5p/CCL20

“…Ang II has a proinflammatory effect and can increase inflammatory markers and the production of free radicals, triggering inflammatory events, which may be the basis of Ang II-mediated induction of AAA. 42 Because ApoE−/− mice lack the ApoE gene and lipids and cholesterol are more likely to accumulate in the aorta, leading to more severe atherosclerosis and inflammation, Ang II-infused ApoE−/− mouse models are commonly used in preclinical AAA studies. 43 Our study showed that the aortic wall was damaged and elastin was degraded in the AAA group.…”

Targeting metabolism in aortic aneurysm and dissection: from basic research to clinical applications

“…In consequence, pro-inflammatory AA seems to play an important role in AAD. The pro-inflammatory response observed in AAD could be due to the lack of anti-inflammatory AA results 107 . Therefore, it is necessary to investigate whether the combined application of PUFA is more suitable for the prevention of AAD in humans.…”

“…Low serum EPA levels and EPA/AA ratio were associated with the size and growth rate of AAA [121]. The protective effects and underlying mechanisms of EPA in AAA have been identified (Figure 4): (1) increased anti-inflammatory property of macrophages due to lessened inflammatory factor such as MMP2 and MMP9 levels [122][123][124] (2) attenuated of mesenchymal stem cell (MSC) dysfunctions [125] (3) suppressed the weakening of the vascular wall by inhibiting the elastin fiber degradation caused by nicotine [126] (4) inhibition of endothelial cell-mediated inflammatory factors [107]. AAA is associated with inflammation and oxidative stress, the latter of which contributes to activation of macrophages, a prominent cell type in AAA.…”