The mechanism and therapy of aortic aneurysms

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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. [1] 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.

Targeting the apoptosis ofvascular smooth muscle cells (VSMCs) is one of the strategies to treat AA. Transcription factor EB (TFEB) can inhibit apoptosis but is downregulated in the tissues of AA patients. 2-Hydroxypropyl-β-cyclodextrin (HPβCD) can activate TFEB and inhibit AA in a mouse model and is a potential clinical therapeutic agent. [2]

[1] Gao, J., Cao, H., Hu, G. et al. The mechanism and therapy of aortic aneurysms. Sig Transduct Target Ther 8, 55 (2023).

[2] Lu H, Sun J, Liang W, Chang Z, Rom O, Zhao Y, Zhao G, Xiong W, Wang H, Zhu T, Guo Y, Chang L, Garcia-Barrio MT, Zhang J, Chen YE, Fan Y. Cyclodextrin Prevents Abdominal Aortic Aneurysm via Activation of Vascular Smooth Muscle Cell Transcription Factor EB. Circulation. 2020 Aug 4;142(5):483-498. doi: 10.1161/CIRCULATIONAHA.119.044803.

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