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ASSA13-11-1 Correlation Analysis and Mechanism Study Between Autoantibodies Against Angiotension AT1 Receptor and Inflammation in Atherosclerosis
  1. Sun Yanxiang,
  2. Yuan Yong,
  3. Feng Li,
  4. Ma Shihui,
  5. Dong Jianting,
  6. Huang Xuansheng,
  7. Zhang Liting,
  8. Tao Jun,
  9. Wang Yan
  1. Department of Cardiology, Zhongshan Hospital, Sun Yat-Sen University, Guangdong

Abstract

Background and Objective Some studies have demonstrated the autoantiboies have an agonist-like activity effect similar to angiotensin II and are involved in the immunopathogenesis of hypertension. We investigate the effect of AT1-AAs on inflammation in atherosclerosis rabbit.

Methods AT1-AAs were purified from sera of patients with primary hypertension by affinity chromatography. We built rabbit atherosclerosis model by abdominal aorta balloon angioplasty with high-fat diet. 30 rabbits were randomly divided into six groups: group control (injected intravenously with PBS), group injected intravenously by AT1-AAs with low dose and group by AT1-AAs with high dose, group AT1-AAs with losartan, group AT1-AAs with simvastatin and group AT1-AAs with 7aa (losartan and simvastatin by intragastric administration). The levels of AT1-AAs, TNF-a and IL-6 in different stage were detected by ELISA. The relationships among AT1-AAs, TNF-a and IL-6 were analysed by multiple linear regressions. After 10 weeks, the rabbits were killed. Their abdominal aortas were taken out and stained with HE. Image-Pro Express system was used to measure the percentage of atheromatous plaques in the area of lumen. The expression of MMP-2 inaortic tissue was detected by Western blotting.

Results The levels of AT1-AAs in the eighth week (W8th) and the tenth week (W10th) week were significantly higher than the beginning of test (W0th) in all groups excluding control one (Fig1). In addition, the values of total cholesterol (TC) and low density lipoprotein (LDL) were obviously high in W4th week (data not shown). The level of TNF-a of W8th (0.173 ± 0.043, 0.435 ± 0.082) and W10th (0.233 ± 0.042, 0.839 ± 0.109) week were significantly higher than W0th week (0.042 ± 0.027, 0.078 ± 0.022) in the group of AT1-AAs with low dose and high dose (all P < 0.05). The level of IL-6 stimulated by high dose AT1-AAs was higher in W10th (0.418 ± 0.077) than W0th (0.039 ± 0.010), P < 0.05. The expression of TNF-a and IL-6 was significantly positive relative to prevalence of AT1-AAs in group of low doze and high doze AT1-AAs. The expression of TNF-a and IL-6 inelse groups were not significant difference in different stage (Fig2 and Fig3).

Abstract ASSA13-11-1 Figure 1

The levels of AT1-AAs in different times.

C: control group; LA: AT1-AAs with low dose; HA: AT1-AAs with high dose; L: losartan; S: simvastatin; 7aa: a inhibitor peptide of AT1-AAs.

Abstract ASSA13-11-1 Figure 2-3

The level of TNF-α and IL-6 in different stage with different groups.

The relative plaque area was significantly increased in group AT1-AAs with low dose (46.99% ± 13.06%) and high dose (66.11% ± 19.67%) compared with in group control (27.71% ± 7.46%), group AT1-AAs with losartan (34.27% ± 12.38%), group AT1-AAs with simvastatin (24.03% ± 8.56%) and group AT1-AAs with 7aa (28.54% ± 12.50%), all P < 0.05 (Fig4). The expression of MMP-2 was higher in group AT1-AAs with low dose (0.419 ± 0.032) and high dose (0.535 ± 0.038) than in other groups, P < 0.05 (Fig5).

Abstract ASSA13-11-1 Figure 4

(×200) The relative plaque area was significantly increased in group LA and HA compared with other groups, all P < 0.05.

Abstract ASSA13-11-1 Figure 5

The expression of MMP-2 was higher in group HA and LA than in other groups, *P < 0.05.

Conclusions The AT1-AAs accerelate the atheromatous plaque formation in rabbit atherosclerosis model by aorta balloon angioplasty and aggravate the inflammatory reaction in local plaque.

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