Xianhua Zhu1, Ping Wu2, Jiehua Qiu3, Li Li1*
1Department of Vascular surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China - 2Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China - 3Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
Objective: To analyse the mechanism of angiotensin receptor antagonist-mediated repair of the aorta in rats with aortic dissection through regulation of Smad2 / Smad4 proteins.
Methods: Thirty 14-day-old pregnant rats were selected, of which 20 were administrated hydroxyethylene diamine at 150 mg/kg/day by gavage to induce the development of offspring with aortic dissection. The neonatal rats were randomly assigned to the losartan group or model group, with 10 rats per group. Rats in the losartan group were administered losartan, an angiotensin receptor antagonist, at a dose of 20 mg/kg/day by gavage. The model group was administered the same amount of normal saline by gavage. The remaining 10 healthy neonatal rats were assigned to the normal group and were administered the same amount of normal saline. The aortas of each group of rats were evaluated using HE staining. The inner diameters of the ascending aorta, aortic arch, and descending aorta were measured by ultrasound. The expression of TGF-β1, Smad2, and Smad4 proteins were detected by Western blot.
Results: In the model group, the rats experienced an intimal tear of the aorta and the middle layer was filled with red blood cells. In the losartan group, a hematoma was formed in the middle layer of the aorta, which was more intact than in the model group, and the tear healed. The inner diameters of ascending aorta, aortic arch, and descending aorta of rats in the losartan group were significantly smaller than those of the model group (P<0.05), but there was no statistically significant difference in the mean inner diameter of each vessel (P>0.05). The TGF-β1 protein content of the aortic vessels of the losartan group was significantly lower than that of the model group (P<0.01). The Smad2 and Smad4 protein content of the aortas of rats in the losartan group was significantly lower than in the model group (P<0.01).
Conclusion: Angiotensin receptor antagonists have obvious protective effects on the damaged aortas of rats with aortic dissection. The underlying mechanism may be the angiotensin receptor antagonist-mediated inhibition of the TGF-β1 pathway and reduction in production of downstream proteins Smad2 and Smad4, thereby controlling the expansion and progression of aortic dissection.
Angiotensin receptor antagonists, TGF-β1, Smad2, Smad4, aortic dissection, vascular wall.