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. 2019 May;244(7):612-620.
doi: 10.1177/1535370219840981. Epub 2019 Apr 26.

Effect of Irbesartan on AGEs-RAGE and MMPs systems in rat type 2 diabetes myocardial-fibrosis model

Ye Hongwei  1   2 , Cao Ruiping  1   2 , Fang Yingyan  3 , Zhang Guanjun  1 , Hu Jie  1 , Liu Xingyu  1 , Tang Jie  2 , Li Zhenghong  1 , Gao Qin  1 , Hu Junfeng  4 , Zhang Heng  5
Affiliations

Effect of Irbesartan on AGEs-RAGE and MMPs systems in rat type 2 diabetes myocardial-fibrosis model

Ye Hongwei et al. Exp Biol Med (Maywood). 2019 May.

Abstract

There are about 425 million diabetes patients (20-79 years) in the world according to the International Diabetes Federation Diabetes Atlas - 8th Edition. The cardiovascular complication is one of the major causes of death in diabetes patients. Myocardial fibrosis is one of the serious pathological changes, so investigating the pathogenesis of myocardial fibrosis has the significant value. Our study aims to investigate the effect of Irbesartan (the angiotensin II receptor antagonist) on the changes of AGE-RAGE system and MMP family components, and analyzes the potential mechanisms in type 2 diabetes-induced myocardial fibrosis. Our results provide the theoretical base for better understanding the pathogenesis in type 2 diabetes-induced myocardial complication. It is useful for clinicians to select the effective therapeutic measures for treatment of type 2 diabetes-induced organ fibrosis.

Keywords: Irbesartan; Type 2 diabetes mellitus; advanced glycation end products and their receptor system; matrix metalloproteinases pathway; myocardial fibrosis.

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Figures

Figure 1.
Figure 1.
Changes of myocardial interstitial and perivascular fibrosis in different groups (Original magnification: × 100). (a) control group (CON); (b) high glucose and high-caloric diet group (HC); (c) Type 2 diabetes mellitus mimic model group (T2DM); (d) Irbesartan + Type 2 diabetes mellitus mimic model group (Ir+ T2DM).
Figure 2.
Figure 2.
Changes of cardiac col I protein expression in different groups (a) and the ratio of col I/β-actin (b). CON: control group; HC: high glucose and high caloric diet group; T2DM: Type 2 Diabetes mellitus mimic model group; Ir+ T2DM: Irbesartan + Type 2 Diabetes mellitus mimic model group. **P < 0.01 vs CON; ##P < 0.01 vs T2DM; ^^P < 0.01 vs HC.
Figure 3.
Figure 3.
Changes of cardiac AGE and RAGE protein expressions in different groups (a), the ratio of AGE/β-actin (b), and the ratio of RAGE/β-actin (c). CON: control group; HC: high glucose and high caloric diet group; T2DM: Type 2 Diabetes mellitus mimic model group; Ir+ T2DM: Irbesartan + Type 2 Diabetes mellitus mimic model group. *P < 0.05, **P < 0.01 vs CON; ##P < 0.01 vs T2DM; ^^P < 0.01 vs HC.
Figure 4.
Figure 4.
Changes of cardiac MMP-14, MMP-2 and TIMP-2 protein expressions in different groups (a), the ratio of MMP-2/β-actin (b), the ratio of TIMP-2/β-actin (c), the ratio of MMP-14/β-actin (d), the ratio of MMP-2/TIMP-2 (e) and the ratio of MMP-14/TIMP-2 (f) in different groups by western blot. CON: control group; HC: high glucose and high caloric diet group group; T2DM: Type 2 Diabetes mellitus mimic model group; Ir+ T2DM: Irbesartan + Type 2 Diabetes mellitus mimic model group. *P < 0.05, **P < 0.01 vs CON; #P < 0.05 and ##P < 0.01 vs T2DM; ^^P < 0.01 vs HC.
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