Invited commentary

Abstract

Abdominal aortic aneurysm (AAA) accounts for >20 million deaths worldwide.1Golledge J. Norman P.E. Murphy M.P. Dalman R.L. Challenges and opportunities in limiting abdominal aortic aneurysm growth.J Vasc Surg. 2017; 65: 225-233Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar Extrapolating from the National Inpatient Sample data set capturing 20% of inpatients in the United States, approximately 500,000 operations for AAA were performed from 2000 to 2010.2Dua A. Ali F. Traudt E. Desai S.S. Utilization of the National Inpatient Sample for abdominal aortic aneurysm research.Surgery. 2017; 162: 699-706Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar The number of aneurysms fixed by endovascular aneurysm repair increased from 5% to approximately 75% during that period, with concomitant improvements in mortality and morbidity within 2 to 3 years of surgery.2Dua A. Ali F. Traudt E. Desai S.S. Utilization of the National Inpatient Sample for abdominal aortic aneurysm research.Surgery. 2017; 162: 699-706Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar, 3Weinkauf C. George E. Zhou W. Open versus endovascular aneurysm repair trial review.Surgery. 2017; 162: 974-978Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar Similar to the advancements offered by endovascular aneurysm repair, medical treatments that could reduce the growth rate of AAA even modestly would save lives and radically alter clinical practice. Perhaps research in this area truly represents an opportunity to “work ourselves out of a job” toward the benefit of patients' well-being. Thus, we continue to strive for a medical treatment that reduces AAA growth rate in the face of disappointing results associated with promising agents like doxycycline.4Meijer C. Stijnen T. Wasser M.M. Hamming J.F. van Bockel J.H. Lindeman J.H. Pharmaceutical Aneurysm Stabilisation Trial Study GroupDoxycycline for stabilization of abdominal aortic aneurysms: a randomized trial.Ann Intern Med. 2013; 159: 815-823Crossref PubMed Scopus (146) Google Scholar The report by Tsai et al evaluates benefits of fucoidan, an extract from brown seaweed, in reducing experimentally induced AAA in mice. The authors report a premise to study fucoidan in cardiovascular disease because of its anti-inflammatory, anticoagulant, and antihypertensive effects. The investigators demonstrate that in a murine model of AAA induced by infusing angiotensin II through a subcutaneous pump, aortic diameter was reduced by intraperitoneal administration of fucoidan. Treatment also mitigated degradation of aortic elastin, diminished inflammatory cell recruitment, and reduced the activities of matrix metalloproteinases (MMPs) thought to degrade extracellular matrix. In human umbilical vein endothelial cells, fucoidan also reduced MMP activity as well as reactive oxygen species expression. The authors conclude that whereas more research needs to be done, fucoidan may be a promising supplement for patients with small aneurysms. There are a few questions that emerge from the report that are worth investigating. It is not clear from the study what role inflammatory cells play in the protective process. Does the fucoidan limit elastin degradation because of a direct effect on elastin or because of an effect on inflammatory cells? Is it relevant to evaluate MMP activity and reactive oxygen species in human umbilical vein endothelial cells when the model is a murine model of aortic disease? Do angiotensin II infusion models of AAA adequately reflect the human condition that typically takes years to develop and is multifactorial? Finally, how would fucoidan be given to a patient? Could it be an oral supplement, or would it need to be administered parenterally, and if so, how often? The authors have alluded to these limitations and have committed to pursuing some of the answers in future studies. While research into aneurysm growth retardants continues, we can only offer surveillance until the aortic diameter thresholds warrant repair. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. Fucoidan attenuates angiotensin II-induced abdominal aortic aneurysms through the inhibition of c-Jun N-terminal kinase and nuclear factor κB activationJournal of Vascular SurgeryVol. 68Issue 6PreviewRupture of abdominal aortic aneurysm (AAA) is one of the leading causes of sudden death among the elderly. Most incidental AAAs are below the threshold for intervention at the time of detection; however, there is no evidence that commonly used cardiovascular drugs have clinical beneficial effects on AAA progression. Therefore, in addition to current cardiovascular risk-reducing treatments, an adjunctive medical therapy targeting the regulation of extracellular matrix metabolism is still required in the clinical setting. Full-Text PDF Open Archive