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European Heart Journal Aug 2023Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in... (Review)
Review
Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in men) are monitored by imaging and large asymptomatic, symptomatic, and ruptured AAAs are considered for surgical repair. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. This review outlines research on AAA pathogenesis and therapies to limit AAA growth. Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. Mendelian randomization analyses suggest that treatments to reduce low-density lipoprotein cholesterol such as proprotein convertase subtilisin/kexin type 9 inhibitors and smoking reduction or cessation are also treatment targets. Thirteen placebo-controlled randomized trials have tested whether a range of antibiotics, blood pressure-lowering drugs, a mast cell stabilizer, an anti-platelet drug, or fenofibrate slow AAA growth. None of these trials have shown convincing evidence of drug efficacy and have been limited by small sample sizes, limited drug adherence, poor participant retention, and over-optimistic AAA growth reduction targets. Data from some large observational cohorts suggest that blood pressure reduction, particularly by angiotensin-converting enzyme inhibitors, could limit aneurysm rupture, but this has not been evaluated in randomized trials. Some observational studies suggest metformin may limit AAA growth, and this is currently being tested in randomized trials. In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.
Topics: Male; Humans; Female; Prospective Studies; Genome-Wide Association Study; Anti-Bacterial Agents; Aneurysm, Ruptured; Aortic Aneurysm, Abdominal; Aortic Rupture
PubMed: 37387260
DOI: 10.1093/eurheartj/ehad386 -
Signal Transduction and Targeted Therapy Feb 2023Aortic aneurysm is a chronic aortic disease affected by many factors. Although it is generally asymptomatic, it poses a significant threat to human life due to a high... (Review)
Review
Aortic aneurysm is a chronic aortic disease affected by many factors. Although it is generally asymptomatic, it poses a significant threat to human life due to a high risk of rupture. Because of its strong concealment, it is difficult to diagnose the disease in the early stage. At present, there are no effective drugs for the treatment of aneurysms. Surgical intervention and endovascular treatment are the only therapies. Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm, the specific mechanisms remain unclear. Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment. To better understand aortic aneurysm, this review elaborates on the discovery history of aortic aneurysm, main classification and clinical manifestations, related molecular mechanisms, clinical cohort studies and animal models, with the ultimate goal of providing insights into the treatment of this devastating disease. The underlying problem with aneurysm disease is weakening of the aortic wall, leading to progressive dilation. If not treated in time, the aortic aneurysm eventually ruptures. An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall. The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.
Topics: Animals; Humans; Aortic Aneurysm, Abdominal; Aortic Rupture; Cohort Studies
PubMed: 36737432
DOI: 10.1038/s41392-023-01325-7 -
Circulation Jan 2020Sporadic aortic aneurysm and dissection (AAD), caused by progressive aortic smooth muscle cell (SMC) loss and extracellular matrix degradation, is a highly lethal...
BACKGROUND
Sporadic aortic aneurysm and dissection (AAD), caused by progressive aortic smooth muscle cell (SMC) loss and extracellular matrix degradation, is a highly lethal condition. Identifying mechanisms that drive aortic degeneration is a crucial step in developing an effective pharmacologic treatment to prevent disease progression. Recent evidence has indicated that cytosolic DNA and abnormal activation of the cytosolic DNA sensing adaptor STING (stimulator of interferon genes) play a critical role in vascular inflammation and destruction. Here, we examined the involvement of this mechanism in aortic degeneration and sporadic AAD formation.
METHODS
The presence of cytosolic DNA in aortic cells and activation of the STING pathway were examined in aortic tissues from patients with sporadic ascending thoracic AAD. The role of STING in AAD development was evaluated in -deficient () mice in a sporadic AAD model induced by challenging mice with a combination of a high-fat diet and angiotensin II. We also examined the direct effects of STING on SMC death and macrophage activation in vitro.
RESULTS
In human sporadic AAD tissues, we observed the presence of cytosolic DNA in SMCs and macrophages and significant activation of the STING pathway. In the sporadic AAD model, mice showed significant reductions in challenge-induced aortic enlargement, dissection, and rupture in both the thoracic and abdominal aortic regions. Single-cell transcriptome analysis revealed that aortic challenge in wild-type mice induced the DNA damage response, the inflammatory response, dedifferentiation and cell death in SMCs, and matrix metalloproteinase expression in macrophages. These changes were attenuated in challenged mice. Mechanistically, nuclear and mitochondrial DNA damage in SMCs and the subsequent leak of DNA to the cytosol activated STING signaling, which induced cell death through apoptosis and necroptosis. In addition, DNA from damaged SMCs was engulfed by macrophages in which it activated STING and its target interferon regulatory factor 3, which directly induced matrix metalloproteinase-9 expression. We also found that pharmacologically inhibiting STING activation partially prevented AAD development.
CONCLUSIONS
Our findings indicate that the presence of cytosolic DNA and subsequent activation of cytosolic DNA sensing adaptor STING signaling represent a key mechanism in aortic degeneration and that targeting STING may prevent sporadic AAD development.
Topics: Aortic Dissection; Animals; Aortic Rupture; Cytosol; DNA; Female; Male; Membrane Proteins; Mice; Mice, Knockout; Signal Transduction
PubMed: 31887080
DOI: 10.1161/CIRCULATIONAHA.119.041460 -
Deutsches Arzteblatt International Oct 2020
Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Humans
PubMed: 33568257
DOI: 10.3238/arztebl.2020.0811 -
Deutsches Arzteblatt International Oct 2020This review presents the surgical indications, surgical procedures, and results in the treatment of asymptomatic and ruptured abdominal aortic aneurysms (AAA). (Review)
Review
BACKGROUND
This review presents the surgical indications, surgical procedures, and results in the treatment of asymptomatic and ruptured abdominal aortic aneurysms (AAA).
METHODS
An updated search of the literature on screening, diagnosis, treatment, and follow-up of AAA, based on the German clinical practice guideline published in 2018.
RESULTS
Surgery is indicated in men with an asymptomatic AAA ≥ 5.5 cm and in women, ≥ 5.0 cm. The indication in men is based on four randomized trials, while in women the data are not conclusive. The majority of patients with AAA (around 80%) meanwhile receive endovascular treatment (endovascular aortic repair, EVAR). Open surgery (open aneurysm repair, OAR) is reserved for patients with longer life expectancy and lower morbidity. The pooled 30-day mortality is 1.16% (95% confidence interval [0.92; 1.39]) following EVAR, 3.27% [2.7; 3.83] after OAR. Women have higher operative/interventional mortality than men (odds ratio 1.67%). The mortality for ruptured AAA is extremely high: around 80% of women and 70% of men die after AAA rupture. Ruptured AAA should, if possible, be treated via the endovascular approach, ideally with the patient under local anesthesia. Treatment at specialized centers guarantees the required expertise and infrastructure. Long-term periodic monitoring by mean of imaging (duplex sonography, plus computed tomography if needed) is essential, particularly following EVAR, to detect and (if appropriate) treat endoleaks, to document stable diameter of the eliminated aneurysmal sac, and to determine whether reintervention is necessary (long-term reintervention rate circa 18%).
CONCLUSION
Vascular surgery now offers a high degree of safety in the treatment of patients with asymptomatic AAA. Endovascular intervention is preferred.
Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Endovascular Procedures; Female; Humans; Male; Odds Ratio; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 33568258
DOI: 10.3238/arztebl.2020.0813 -
Scandinavian Journal of Surgery : SJS :... Jun 2021Acute mesenteric ischemia is considered uncommon, but it appears to be more frequent cause of acute abdomen than appendicitis or ruptured abdominal aortic aneurysm in... (Review)
Review
Acute mesenteric ischemia is considered uncommon, but it appears to be more frequent cause of acute abdomen than appendicitis or ruptured abdominal aortic aneurysm in elderly patients. Surgical treatment without revascularization is associated with high overall mortality, up to 80%. The modern treatment of acute mesenteric ischemia requires collaboration of gastrointestinal surgeons, vascular surgeons, and interventional radiologists. Early revascularization may reduce the overall mortality associated with acute mesenteric ischemia by up to 50%. Clinical suspicion and contrast-enhanced computed tomography performed at early stage are keys to improve outcomes of acute mesenteric ischemia treatment. This review summarizes what the acute care surgeon needs to know about acute mesenteric ischemia with special emphasis on slowly progressing "acute on chronic" mesenteric ischemia.
Topics: Acute Disease; Aged; Aortic Rupture; Humans; Ischemia; Mesenteric Ischemia; Surgeons; Vascular Surgical Procedures
PubMed: 33866891
DOI: 10.1177/14574969211007590 -
Frontiers in Cardiovascular Medicine 2023
PubMed: 36818356
DOI: 10.3389/fcvm.2023.1137949 -
Clinical Science (London, England :... Aug 2023Abdominal aortic aneurysm (AAA) is a severe vascular disease and a major public health issue with an unmet medical need for therapy. This disease is featured by a... (Review)
Review
Abdominal aortic aneurysm (AAA) is a severe vascular disease and a major public health issue with an unmet medical need for therapy. This disease is featured by a progressive dilation of the abdominal aorta, boosted by atherosclerosis, ageing, and smoking as major risk factors. Aneurysm growth increases the risk of aortic rupture, a life-threatening emergency with high mortality rates. Despite the increasing progress in our knowledge about the etiopathology of AAA, an effective pharmacological treatment against this disorder remains elusive and surgical repair is still the unique available therapeutic approach for high-risk patients. Meanwhile, there is no medical alternative for patients with small aneurysms but close surveillance. Clinical trials assessing the efficacy of antihypertensive agents, statins, doxycycline, or anti-platelet drugs, among others, failed to demonstrate a clear benefit limiting AAA growth, while data from ongoing clinical trials addressing the benefit of metformin on aneurysm progression are eagerly awaited. Recent preclinical studies have postulated new therapeutic targets and pharmacological strategies paving the way for the implementation of future clinical studies exploring these novel therapeutic strategies. This review summarises some of the most relevant clinical and preclinical studies in search of new therapeutic approaches for AAA.
Topics: Humans; Aortic Aneurysm, Abdominal; Aorta, Abdominal; Doxycycline; Aortic Rupture; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 37559446
DOI: 10.1042/CS20220795 -
Experimental & Molecular Medicine Dec 2023Aortic aneurysm is a chronic disease characterized by localized expansion of the aorta, including the ascending aorta, arch, descending aorta, and abdominal aorta.... (Review)
Review
Aortic aneurysm is a chronic disease characterized by localized expansion of the aorta, including the ascending aorta, arch, descending aorta, and abdominal aorta. Although aortic aneurysms are generally asymptomatic, they can threaten human health by sudden death due to aortic rupture. Aortic aneurysms are estimated to lead to 150,000 ~ 200,000 deaths per year worldwide. Currently, there are no effective drugs to prevent the growth or rupture of aortic aneurysms; surgical repair or endovascular repair is the only option for treating this condition. The pathogenic mechanisms and therapeutic targets for aortic aneurysms have been examined over the past decade; however, there are unknown pathogenic mechanisms involved in cellular heterogeneity and plasticity, the complexity of the transforming growth factor-β signaling pathway, inflammation, cell death, intramural neovascularization, and intercellular communication. This review summarizes the latest research findings and current pathogenic mechanisms of aortic aneurysms, which may enhance our understanding of aortic aneurysms.
Topics: Humans; Aortic Aneurysm, Thoracic; Chronic Disease; Aortic Rupture; Aorta
PubMed: 38036736
DOI: 10.1038/s12276-023-01130-w