Role of angiotensin II type 1 receptor agonistic autoantibody in cardiac hypertrophy of hyperthyroidism rats and its relationship with PI3K/Akt signaling pathway / 第二军医大学学报

ABSTRACT

Objective To investigate the serum level of angiotensin II type 1 receptor (AT1R) agonistic autoantibody (AT1-AA) in hyperthyroidismratswith cardiac hypertrophy and the expression of PI3K and protein kinase B (Akt) in cardiac tissue, so as to study the relationship between AT1-AA and PI3K/Akt signaling pathway. Methods Hyperthyroidism rats models were established by gavaging with levothyroxine sodium. Totally 54 SD rats were divided into three groups hyperthyroidism group (group A), hyperthyroidism+ olmesartan group (group B) and control group (group C). The heart weight index (HWI) and atrial natriuretic peptide (ANP) mRNA were taken as the indices for cardiac hypertrophy. Serum AT1-AA level was determined by enzyme-linked immunosorbent assay (ELISA), and the expression of ATiR and PI3K/Akt was detected by Western blotting analysis. According to the determination results of AT1-AA, group A and B rats were subdivided into AT1-AA positive group and negative group; the expressions of AT1R and PI3K/Akt were compared between these groups. Results (1) Compared with group C, HWI and the expression of ANP mRNA in group A and B were significantly increased (all P<0. 05); and those in group A were significantly higher than those in group B (P<0. 05). (2) The positive rates and OD values of AT1-AA in group A and B (61.11%, 72. 22% and 0. 44±0. 12, 0. 49 ±0. 08) were significantly higher than those in group C (16. 67% and 0. 28±0. 05) (all P<0. 01). (3)The expressions of AT1R and PI3K/p-Akt in group A and B were significantly higher than those in group C (P<0. 05, P<0. 01). Compared with group A, the expression levels of PI3K, p-Akt were significantly decreased in group B (P<0. 01, P<0. 05). (4) In group A, the expression levels of PI3K and p-Akt in AT1-AA positive group were significantly higher than those in AT1-AA negative group(P<0. 01); in group B, the expression levels of PI3K and p-Akt in AT1-AA positive group were significantly decreased than those in AT1-AA negative group (P<0. 05). Conclusion AT1-AA may be involved in the pathophysiology of cardiac hypertrophy in hyperthyroidism by activating PI3K/Akt signaling pathway through AT1R.