Roles and possible mechanisms of autoantibodies against the angiotensin AT1 receptor in vascular calcification of rats

The aim of this study was to investigate the effect of AT1-AAs on vascular calcification. Wistar rats were immunized with synthetic peptides corresponding to the second extracellular loop of AT1 receptor. The titer of AT1-AAs in rat serum, SBP, and HR were detected weekly. Histological analysis and biochemical parameters were measured 4 months after initial immunization. The level of osteopontin and osteocalcin was measured by Western blot analysis. The results showed that the titer of AT1-AAs, SBP, and HR were all increased significant 4 weeks after initial immunization. Compared with the control group, the contractile force of the aortic ring of the immunized group to phenylephrine was significantly higher, and relaxation function was significantly reduced. The ALP activ- ity and protein levels of osteoporotin and osteocalcin were increased in the aortic tissue of the immunized group. Histological examination showed varying degrees of calcification within each cell layer with von Kossa staining in the immunized group. Losartan treatment not only significantly lowered SBP and HR to the similar level of the control group but inhibited the ALP activity and protein levels of osteoporotin and osteocalcin. Our study demonstrated that AT1-AAs contributed to the progression of vascular calcification, suggesting that AT1-AAs may play a vital role in the occurrence of cardiovascular disease in patients with severe hypertension.