Shih-Hung Tsai1, Jen-Chun Wang2, Wen-I Liao3, Yu-Juei Hsu4, Chih-Yuan Lin5, Min-Tser Liao6, Po-Hsun Huang7, Shing-Jong Lin7. 1. Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address: tsaishihung@yahoo.com.tw. 2. Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. 3. Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 4. Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 5. Division of Cardiovascular Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 6. Department of Pediatrics, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan. 7. Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
Abstract
BACKGROUND: Rupture 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. Fucoidan is an extract of brown seaweed and a sulfated polysaccharide. Emerging evidence suggests that fucoidan has potential cardiovascular applications. Numerous investigations of fucoidan in diseases of the cardiovascular system have mainly focused on its pleiotropic anti-inflammatory effects. Specifically, fucoidan has been shown to have matrix metalloproteinase (MMP)-reducing effects in several studies. We aimed to evaluate the beneficial effect of fucoidan on aneurysmal growth in a murine model of aortic aneurysm and further provide a rationale for using fucoidan as a medical adjunctive therapy. METHODS: A murine model of angiotensin II (Ang II)-induced AAA was used to assess the therapeutic effects of fucoidan on AAA growth in vivo. The characteristics and quantification of AAAs were determined in situ. Human umbilical vein endothelial cells were used for studying the involved pathways in vitro. Western blotting was used to detect the involved signaling pathways both in vivo and in vitro. RESULTS: Treatment with fucoidan significantly reduced the incidence of AAA formation. Administration of fucoidan significantly attenuated Ang II-induced aortic expansion from 1.56 ± 0.76 mm to 1.09 ± 0.30 mm. Administration of fucoidan significantly suppressed MMP-2 and MMP-9 activities and reduced the grade of elastin degradation in vivo. In vitro, we found that fucoidan could ameliorate the Ang II-induced phosphorylation of c-Jun N-terminal kinase and nuclear factor κB p65, and it further reduced MMP and reactive oxygen species production. CONCLUSIONS: Fucoidan inhibits the progression of experimental AAA growth through the attenuation of proinflammatory nuclear factor κB and c-Jun N-terminal kinase activation. Fucoidan could be a potential medical adjunctive therapy for small AAAs.
BACKGROUND: Rupture 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. Fucoidan is an extract of brown seaweed and a sulfated polysaccharide. Emerging evidence suggests that fucoidan has potential cardiovascular applications. Numerous investigations of fucoidan in diseases of the cardiovascular system have mainly focused on its pleiotropic anti-inflammatory effects. Specifically, fucoidan has been shown to have matrix metalloproteinase (MMP)-reducing effects in several studies. We aimed to evaluate the beneficial effect of fucoidan on aneurysmal growth in a murine model of aortic aneurysm and further provide a rationale for using fucoidan as a medical adjunctive therapy. METHODS: A murine model of angiotensin II (Ang II)-induced AAA was used to assess the therapeutic effects of fucoidan on AAA growth in vivo. The characteristics and quantification of AAAs were determined in situ. Human umbilical vein endothelial cells were used for studying the involved pathways in vitro. Western blotting was used to detect the involved signaling pathways both in vivo and in vitro. RESULTS: Treatment with fucoidan significantly reduced the incidence of AAA formation. Administration of fucoidan significantly attenuated Ang II-induced aortic expansion from 1.56 ± 0.76 mm to 1.09 ± 0.30 mm. Administration of fucoidan significantly suppressed MMP-2 and MMP-9 activities and reduced the grade of elastin degradation in vivo. In vitro, we found that fucoidan could ameliorate the Ang II-induced phosphorylation of c-Jun N-terminal kinase and nuclear factor κB p65, and it further reduced MMP and reactive oxygen species production. CONCLUSIONS:Fucoidan inhibits the progression of experimental AAA growth through the attenuation of proinflammatory nuclear factor κB and c-Jun N-terminal kinase activation. Fucoidan could be a potential medical adjunctive therapy for small AAAs.