The mechanism and therapy of aortic aneurysms

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.

Induction of thoracic aortic dissection: a mini-review of β-aminopropionitrile-related mouse models

Thoracic aortic dissection(TAD)is one of the most lethal aortic diseases due to its acute onset,rapid progress,and high rate of aortic rupture.The pathogenesis of TAD is not completely understood.In this mini-review,we introduce three emerging experimental mouse TAD models usingβ-aminopropionitrile(BAPN)alone,BAPN for a prolonged duration(four weeks)and then with added infusion of angiotensinⅡ(AngⅡ),or co-administration of BAPN and AngⅡchronically.We aim to provide insights into appropriate application of these three mouse models,thereby enhancing the understanding of the molecular mechanisms of TAD.

Polymersomes scalably fabricated via flash nano- precipitation are non-toxic in non-human primates and associate with leukocytes in the spleen and kidney following intravenous administration

Vesicular nanocarrier formulations confer the ability to deliver hydrophobic and hydrophilic cargos simultaneously to cells of interest in vivo. While liposomal formulations reached the clinic long ago, younger technologies such as polymeric vesicles （polymersomes） have yet to make the transition to clinical approval and use, in part due to difficulties in ensuring their safe and scalable production. In this work, we demonstrate the scalable production of poly（ethylene glycol）-block-poly（propylene sulfide） （PEG-bl-PPS） polymersomes via flash nanoprecipitation, and further show the safe administration of these nanocarriers to mice and non-human primates. In mice, PEG-bl-PPS polymersomes were found to be well tolerated at up to 200 mg/（kg.week）. Following the administration of a more relevant 20 mg/（kg.week） dosage in non-human primates, polymersomes were found to associate with numerous phagocytic immune cell populations, including a remarkable 68% of plasmacytoid dendritic cells and 〉 95% of macrophages in the spleen, while showing no toxicity or abnormalities in the liver, kidney, spleen, or blood. Despite the presence of a dense PEG corona, neither anti-PEG antibodies nor complement activation were detected. This work provides evidence of the translatability of PEG-bI-PPS polymersomes into the clinic for therapeutic applications in humans.

Complex pathologies of angiotensin Ⅱ-induced abdominal aortic aneurysms

Angiotensin II （Angll） is the primary bioactive peptide of the renin angiotensin system that plays a critical role in many cardiovascular diseases. Subcutaneous infusion of Angll into mice induces the development of abdominal aortic aneurysms （AAAs）. Like human AAAs, Angll-induced AAA tissues exhibit progressive changes and considerable heterogeneity. This complex pathology provides an impediment to the quantification of aneurysmal tissue composition by biochemical and immunostaining techniques. Therefore, while the mouse model of Angll-induced AAAs provides a salutary approach to studying the mechanisms of the evolution of AAAs in humans, meaningful interpretation of mechanisms requires consideration of the heterogeneous nature of the diseased tissue.