Astragalus polysaccharides inhibited diabetic cardiomyopathy in hamsters depending on suppression of heart chymase activation.
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.
Chen
Wei
W
Department of Geriatrics, Huashan Hospital, Fudan University School of Medicine, Shanghai 200040, China.
Li
Yi-Ming
YM
Yu
Mao-Hua
MH
D000804:Angiotensin II / Q000032:analysis; D000818:Animals; D027885:Astragalus propinquus; D001786:Blood Glucose / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000201:enzymology; D053818:Chymases / Q000187:drug effects*; D003094:Collagen / Q000032:analysis; D006224:Cricetinae; D048909:Diabetes Complications / Q000188:drug therapy* / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D008074:Lipoproteins / Q000032:analysis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D008517:Phytotherapy; D028321:Plant Preparations / Q000627:therapeutic use*; D011134:Polysaccharides / Q000627:therapeutic use*; D000093422:Glycated Serum Proteins
D001786:Blood Glucose; D001798:Blood Proteins; D006023:Glycoproteins; D008074:Lipoproteins; D028321:Plant Preparations; D011134:Polysaccharides; D000804:Angiotensin II; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D053818:Chymases; D020778:Matrix Metalloproteinase 2; D000093422:Glycated Serum Proteins