Liver-Angiotensinogen Contributes To ?-Aminopropionitrile-Induced Thoracic Aortic Dissection In Mice

Background: Thoracic aortic dissection is triggered by a tear in the intimal layer,causing medial intramural bleeding and followed by a separation of the aortic wall layers.It is one of the most life-threatening aortic diseases,but the pathogenesis has not been completely known.The main therapeutic strategy for thoracic aortic dissection is open surgical repair,which with high death risk.So it is meaningful to reveal the pathogenesis and find the effective medical approaches of thoracic aortic dissection.Methods: Four-week liver-specific angiotensinogen(Liver-AGT)deficient mice and their wild type littermates were fed with ?-aminopropionitrile(BAPN)for 4 weeks to induce thoracic aortic dissection.The differences of the aortic rupture and thoracic aortic lesion rate between these two groups were evaluated.Then we fed 4-week C57BL/6 background male mice with BAPN and losartan or BAPN only,the aortic rupture and thoracic aortic lesion rate were compared.Results:(1)BAPN can induce thoracic aortic dissection in C57BL/6 background immature mice.(2)The aortic rupture and thoracic aortic lesion rate of liver-AGT knock out mice induced by BAPN were decreased compared with their wild type littermates,but there were differences between male and female.The elastin degradation of eachaortic section had no significant difference between liver-AGT knock out mice and their wild type littermates.(3)Losartan can deteriorate BAPN induced aortic rupture and thoracic aortic lesion rate,which was related to losartan dose and usage.Conclusions: Knocking out liver-AGT in mice can significantly improve survival rate and decrease thoracic aortic lesion rate during BAPN administration,but there were differences between genders.Losartan can deteriorate BAPN-induced thoracic aortic dissection and relevant death,which was related to losartan dosage and usage.