Cathepsins: a new culprit behind abdominal aortic aneurysm
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Cathepsins: a new culprit behind abdominal aortic aneurysm Yi Wang, Chaoshu Tang and Yanwen Qin*
Abstract Abdominal aortic aneurysm (AAA) is a fatal disease defined as an abdominal aortic diameter of 3.0 cm or more, where the abdominal aorta exceeds the normal diameter by more than 50%. Histopathological changes of AAA mainly include extracellular matrix (ECM) remodeling at the abdominal aorta wall, but there is lack of specific drugs to treat AAA. Recent studies have reported that lysosomal cathepsins could induce vascular remodeling and AAA formation by regulating vascular inflammation, medial smooth muscle cell apoptosis, neovascularization, and protease expression. Thus, cathepsins are expected to become a new therapeutic target for AAA treatment. Keywords: Abdominal aortic aneurysm, Extracellular matrix, Cathepsins
Review Abdominal aortic aneurysm (AAA) is a fatal disease in which the abdominal aorta diameter is more than 50% its normal diameter, exceeding 3.0 cm [1]. AAA is like a time bomb in the body because the progressive increase in aneurysm size eventually leads to aneurysm rupture and uncontrollable bleeding, resulting in a mortality of 80%. The primary clinical treatments for AAA include open surgical repair and endovascular therapy, but so far there are no specific drugs to prevent or reverse AAA progression. Thus, studying AAA pathogenesis is necessary to explore and identify treatment targets. AAA, a common high-risk vascular disease With the aging of the Chinese population, dietary changes, and new testing methods, the prevalence of AAA has increased dramatically, but there is still no epidemiological data regarding AAA in China. According to published epidemiological data, AAA is the 13th most common fatal disease in the United States. The prevalence of AAA among the US population in those over 65 years old is 8%, and about 25,000 patients undergo AAA repair annually [2-4]. Current AAA treatments include open surgical repair and endovascular therapy, which mainly targets * Correspondence: [email protected] The Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China
aneurysms greater than 5.5 cm in diameter, or rapidly growing aneurysms that are at high risk of rupture. However, AAA screening suggests that more than 90% of AAAs are small aneurysms less than 5.5 cm in diameter, so limiting the expansion of small-diameter aneurysms has become a priority in the treatment strategy for AAA [5]. Results from animal experiments and clinical trials have suggested that doxycycline, roxithromycin [6], statins [7-9], 2,4-thiazolidinedione [10], β-blockers [11], and angiotensin-converting enzyme inhibitors [12] can suppress AAA progression, but further mechanistic studies and long-term, large-scale randomized controlled trials are required to verify the effects of these drugs. AAA is a complex disease caused by various
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