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Astragalus polysaccharides inhibited diabetic cardiomyopathy in hamsters depending on suppression of heart chymase
Wei Chen1, Yi-Ming Li, Mao-Hua Yu
1Department of Geriatrics, Huashan Hospital, Fudan University School of Medicine, Shanghai 200040, China.
Insights
Astragalus polysaccharide (APS) may protect against diabetic cardiomyopathy by suppressing the cardiac chymase-angiotensin II system. This traditional Chinese medicine ingredient reduced key markers of heart damage in diabetic hamsters.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Diabetology
Background:
- Diabetic cardiomyopathy, a complication of diabetes mellitus, significantly increases heart failure risk.
- The local chymase-angiotensin II system is implicated as a key driver in the development of diabetic cardiomyopathy.
- Astragalus polysaccharide (APS), a component of traditional Chinese medicine, is known for its immunomodulatory properties.
Purpose of the Study:
- To investigate the therapeutic effects of APS on diabetic cardiomyopathy.
- To determine if APS modulates the local cardiac chymase-angiotensin II system in a diabetic hamster model.
Main Methods:
- Streptozotocin-induced diabetic hamsters were treated with APS or normal saline (NS) for 10 weeks.
- Evaluated hemodynamic parameters, biochemical markers (insulin, C-peptide, GSP, lipoproteins, myocardial enzymes), and Angiotensin II levels.
- Assessed myocardial collagen, ultrastructure, matrix metalloproteinase (MMP) activity, cardiac chymase and ACE activity/expression, and ERK1/2 phosphorylation.
Main Results:
- APS treatment lowered glycosylated serum protein, lipoproteins, myocardial enzymes, and myocardial Ang II levels.
- APS reduced myocardial collagen expression and MMP activity, while preserving myocardial ultrastructure.
- APS inhibited cardiac chymase activity and expression, and decreased ERK1/2 phosphorylation without altering hemodynamic parameters.
Conclusions:
- APS demonstrates a protective effect against diabetic cardiomyopathy in hamsters.
- The cardioprotective mechanism of APS involves the suppression of the local cardiac chymase-angiotensin II system.
- APS represents a potential therapeutic agent for managing diabetic cardiomyopathy.
Abstract:
Diabetic cardiomyopathy is associated with high morbidity and mortality of heart failure. Overactivation of the local chymase-Ang II system plays a dominant role in diabetic cardiomyopathy. Astragalus polysaccharide (APS) is used in traditional Chinese medicine to boost immunity. To study the effect of APS on local system of chymase-Ang II in diabetic cardiomyopathy, we investigated APS/normal saline (NS)-administrated streptozotocin-induced diabetic hamsters. After APS/NS administration at a dose of 1 g/kg per day for 10 weeks, hemodynamic parameters, levels of insulin (INS), C-peptide (C-P), glycosylated serum protein (GSP), lipoproteins, myocardial enzymes, and Ang II (plasma and myocardial) were tested; myocardial collagen (type I and III), myocardial ultrastructure, and activities of matrix metalloproteinase (MMPs) were measured; activities and expression of cardiac chymase and ACE were detected by using quantitative real-time RT-PCR and RIA; protein expression of cardiac phosphoric extracellular signal-regulated kinase 1/2 (p-ERK1/2) was measured by Western blot. AP-administrated diabetic hamsters had lower levels of GSP, lipoproteins, myocardial enzymes, myocardial Ang II, expression of collagen I and I/ III, activities of pro-MMP-2 and MMP-2, activities and expression of chymase, and expression of p-ERK1/2 than NS-administrated diabetic hamsters and could better protect the myocardial ultrastructure. There was no difference in hemodynamic parameters between two groups. These results indicate that APS could inhibit diabetic cardiomyopathy in hamsters depending on the suppression of the local cardiac chymase-Ang II system.
