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A new appraisal of the management of acute aortic dissection is timely because of recent developments in diagnostic strategies (including biomarkers and imaging), endograft design, and surgical treatment, which have led to a better understanding of the epidemiology, risk factors, and molecular nature of aortic dissection. Although open surgery is the main treatment for proximal aortic repair, use of endovascular management is now established for complicated distal dissection and distal arch repair, and has recently been discussed as a pre-emptive measure to avoid late complications by inducing aortic remodelling.

Objective To assess the three year clinical outcomes and cost effectiveness of a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair for patients with suspected ruptured abdominal aortic aneurysm.Design Randomised controlled trial.Setting 30 vascular centres (29 in UK, one in Canada), 2009-16.Participants 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm, of whom 502 underwent emergency repair for rupture.Interventions 316 patients were randomised to an endovascular strategy (275 with confirmed rupture) and 297 to open repair (261 with confirmed rupture).Main outcome measures Mortality, with reinterventions after aneurysm repair, quality of life, and hospital costs to three years as secondary measures.Results The maximum follow-up for mortality was 7.1 years, with two patients in each group lost to follow-up by three years. After similar mortality by 90 days, in the mid-term (three months to three years) there were fewer deaths in the endovascular than the open repair group (hazard ratio 0.57, 95% confidence interval 0.36 to 0.90), leading to lower mortality at three years (48% v 56%), but by seven years mortality was about 60% in each group (hazard ratio 0.92, 0.75 to 1.13). Results for the 502 patients with repaired ruptures were more pronounced: three year mortality was lower in the endovascular strategy group (42% v 54%; odds ratio 0.62, 0.43 to 0.88), but after seven years there was no clear difference between the groups (hazard ratio 0.86, 0.68 to 1.08). Reintervention rates up to three years were not significantly different between the randomised groups (hazard ratio 1.02, 0.79 to 1.32); the initial rapid rate of reinterventions was followed by a much slower mid-term reintervention rate in both groups. The early higher average quality of life in the endovascular strategy versus open repair group, coupled with the lower mortality at three years, led to a gain in average quality adjusted life years (QALYs) at three years of 0.17 (95% confidence interval 0.00 to 0.33). The endovascular strategy group spent fewer days in hospital and had lower average costs of −£2605 (95% confidence interval −£5966 to £702) (about €2813; $3439). The probability that the endovascular strategy is cost effective was >90% at all levels of willingness to pay for a QALY gain.Conclusions At three years, compared with open repair, an endovascular strategy for suspected ruptured abdominal aortic aneurysm was associated with a survival advantage, a gain in QALYs, similar levels of reintervention, and reduced costs, and this strategy was cost effective. These findings support the increasing use of an endovascular strategy, with wider availability of emergency endovascular repair.Trial registration Current Controlled Trials ISRCTN48334791; ClinicalTrials NCT00746122.

Abdominal aortic aneurysm (AAA) rupture is an important cause of death in adults. Currently, the only treatment for AAA is open or endovascular surgical repair. In most parts of the developed world, AAAs can be identified at an early stage as a result of incidental imaging and screening programmes. Randomized clinical trials have demonstrated that early elective surgical repair of these small AAAs is not beneficial, and an unmet clinical need exists to develop medical therapies for small AAAs that limit or prevent the progressive expansion and rupture of the aneurysm. A large amount of research is currently being performed to increase the understanding of AAA pathogenesis and ultimately lead to the development of medical therapies, such as drug-based and cell-based strategies for this disease. This Review summarizes the latest research findings and current theories on AAA pathogenesis, including discussion of the pros and cons of current rodent models of AAA, and highlights potential medical therapies for AAA, summarizing previous, ongoing and potential clinical trials of medical interventions for small AAAs. This expanding volume of research on AAA is expected to result in a range of novel medical therapies for AAA within the next decade.

Abdominal aortic aneurysm (AAA) is a serious vascular disease which is associated with vascular remodeling. CD38 is a main NAD+-consuming enzyme in mammals, and our previous results showed that CD38 plays the important roles in many cardiovascular diseases. However, the role of CD38 in AAA has not been explored. Here, we report that smooth-muscle-cell-specific deletion of CD38 (CD38SKO) significantly reduced the morbidity of AngII-induced AAA in CD38SKOApoe−/− mice, which was accompanied with a increases in the aortic diameter, medial thickness, collagen deposition, and elastin degradation of aortas. In addition, CD38SKO significantly suppressed the AngII-induced decreases in α-SMA, SM22α, and MYH11 expression; the increase in Vimentin expression in VSMCs; and the increase in VCAM-1 expression in smooth muscle cells and macrophage infiltration. Furthermore, we demonstrated that the role of CD38SKO in attenuating AAA was associated with the activation of sirtuin signaling pathways. Therefore, we concluded that CD38 plays a pivotal role in AngII-induced AAA through promoting vascular remodeling, suggesting that CD38 may serve as a potential therapeutic target for the prevention of AAA.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder characterized by progressive dilation and weakening of the abdominal aortic wall. Despite advances in surgical repair, rupture remains associated with mortality rates exceeding 65%, and no effective pharmacological therapy exists to prevent disease progression. Increasing evidence highlights chronic inflammation, extracellular matrix degradation, and immune dysregulation as central drivers of AAA pathogenesis. Among these mechanisms, the thrombospondin-1 (TSP1)–CD47 signaling axis has emerged as a critical upstream regulator of vascular inflammation. By engaging CD47, TSP1 promotes macrophage activation, impairs efferocytosis, and sustains a self-perpetuating inflammatory loop that accelerates tissue destruction. This positions the TSP1–CD47 pathway as more than a bystander in aneurysm biology, linking immune activation with structural failure of the aortic wall. The therapeutic relevance of this axis is underscored by the development of CD47-targeted agents in oncology, which restore phagocytosis and immune balance. Repurposing such strategies for vascular medicine, in combination with advanced drug delivery systems, offers a promising avenue for disease-modifying therapy in AAA. Notably, two targeted drug delivery approaches have been described: both employ bispecific targeting of CD47 in combination with a macrophage-specific marker, using immunotoxins encapsulated in liposomal carriers to enhance selectivity and therapeutic efficacy. By shifting focus from structural repair to immune modulation, targeting the TSP1–CD47 axis with these strategies has the potential to redefine the clinical management of this condition.

The triggering receptor expressed on myeloid cells 1 (TREM-1) drives inflammatory responses in several cardiovascular diseases but its role in abdominal aortic aneurysm (AAA) remains unknown. Our objective was to explore the role of TREM-1 in a mouse model of angiotensin II-induced (AngII-induced) AAA. TREM-1 expression was detected in mouse aortic aneurysm and colocalized with macrophages. Trem1 gene deletion (Apoe-/-Trem1-/-), as well as TREM-1 pharmacological blockade with LR-12 peptide, limited both AAA development and severity. Trem1 gene deletion attenuated the inflammatory response in the aorta, with a reduction of Il1b, Tnfa, Mmp2, and Mmp9 mRNA expression, and led to a decreased macrophage content due to a reduction of Ly6Chi classical monocyte trafficking. Conversely, antibody-mediated TREM-1 stimulation exacerbated Ly6Chi monocyte aorta infiltration after AngII infusion through CD62L upregulation and promoted proinflammatory signature in the aorta, resulting in worsening AAA severity. AngII infusion stimulated TREM-1 expression and activation on Ly6Chi monocytes through AngII receptor type I (AT1R). In human AAA, TREM-1 was detected and TREM1 mRNA expression correlated with SELL mRNA expression. Finally, circulating levels of sTREM-1 were increased in patients with AAA when compared with patients without AAA. In conclusion, TREM-1 is involved in AAA pathophysiology and may represent a promising therapeutic target in humans.

The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30-49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA.

Human abdominal aortic aneurysms (AAAs) are characterized by increased activity of matrix metalloproteinases (MMP), including MMP-12, alongside macrophage accumulation and elastin degradation, in conjunction with superimposed atherosclerosis. Previous genetic ablation studies have proposed contradictory roles for MMP-12 in AAA development. In this study, we aimed to elucidate if pharmacological inhibition of MMP-12 activity with a phosphinic peptide inhibitor protects from AAA formation and progression in angiotensin (Ang) II-infused Apoe−/− mice. Complimentary studies were conducted in a human ex vivo model of early aneurysm development. Administration of an MMP-12 inhibitor (RXP470.1) protected hypercholesterolemia Apoe−/− mice from Ang II-induced AAA formation and rupture-related death, associated with diminished medial thinning and elastin fragmentation alongside increased collagen deposition. Proteomic analyses confirmed a beneficial effect of MMP-12 inhibition on extracellular matrix remodeling proteins combined with inflammatory pathways. Furthermore, RXP470.1 treatment of mice with pre-existing AAAs exerted beneficial effects as observed through suppressed aortic dilation and rupture, medial thinning, and elastin destruction. Our findings indicate that pharmacological inhibition of MMP-12 activity retards AAA progression and improves survival in mice providing proof-of-concept evidence to motivate translational work for MMP-12 inhibitor therapy in humans.

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammation, matrix degradation and smooth muscle cell (SMC) loss, leading to vessel dilation and rupture, with no current pharmaceutical management options. Since recent studies have highlighted the role of extracellular (ex) nucleic acids in promoting inflammation and tissue damage in cardiovascular conditions, we aimed to characterize the contribution of exDNA and exRNA to AAA pathogenesis and evaluate their potential as therapeutic targets in established disease. Circulating exDNA was elevated in patients and mouse models, while plasma levels of exRNA were not associated with AAA development. When RNase A or DNase I was administered to mice with established disease, the targeted degradation of exRNA, but not exDNA, significantly attenuated aneurysm growth. The RNase A treatment produced systemic anti-inflammatory effects (reduced monocyte/granulocyte count) and showed the potential to improve local vascular conditions by preserving SMC integrity, reducing macrophage infiltration and protease expression. These effects were not observed in DNase I-treated animals. In conclusion, while circulating exDNA showed AAA biomarker potential, targeting exRNA by systemic RNase A treatment effectively mitigated aneurysm progression in established disease through pleiotropic modulation of inflammation and tissue remodeling, presenting a novel and promising therapeutic strategy.

An abdominal aortic aneurysm (AAA) is a localized dilatation of the infrarenal aorta. AAA is a multifactorial disease, and genetic and environmental factors play a part; smoking, male sex and a positive family history are the most important risk factors, and AAA is most common in men >65 years of age. AAA results from changes in the aortic wall structure, including thinning of the media and adventitia due to the loss of vascular smooth muscle cells and degradation of the extracellular matrix. If the mechanical stress of the blood pressure acting on the wall exceeds the wall strength, the AAA ruptures, causing life-threatening intra-abdominal haemorrhage — the mortality for patients with ruptured AAA is 65–85%. Although AAAs of any size can rupture, the risk of rupture increases with diameter. Intact AAAs are typically asymptomatic, and in settings where screening programmes with ultrasonography are not implemented, most cases are diagnosed incidentally. Modern functional imaging techniques (PET, CT and MRI) may help to assess rupture risk. Elective repair of AAA with open surgery or endovascular aortic repair (EVAR) should be considered to prevent AAA rupture, although the morbidity and mortality associated with both techniques remain non-negligible. An abdominal aortic aneurysm (AAA) is an enlargement of the abdominal aorta. As the AAA grows, the aortic wall becomes progressively thin, and the risk of rupture increases; AAA rupture causes severe intra-abdominal haemorrhage and has a very high mortality.