The Distribution Of Angiotensin-converting Enzyme 2 On Various Tissues Of Rats With Metabolic Syndrome

Objective:Angiotensin-converting enzyme 2(ACE2) is a newly described renin-angiotensin system(RAS) component that competes with Angiotensin-converting enzyme(ACE) for angiotensin peptide hydrolysis and therefore may modulate blood pressure.Metabolic syndrome(MS) is associated with increased risk of cardiovascular disease,RAS have a close relationship with MS.The present study was designed to determine the ACE2 in heart,aortic endothelial,lung,liver,pancreas,kidney,testis and brain in the rats with MS.To investigate the relationship among ACE2,ACE, AngiotensinⅡ(AngⅡ) and indexes of MS.Methods:Twenty adult healthy male specific pathogen free(SPF) Wister rats were divided randomly as control group(normal diet+ordinary tap water,n=10) and fructose-induced MS group(normal diet+30%-fructose solution,n=10).At week sixth, when model creation were expected to complete,the level of triglyeride(TG),free fatty acid(FFA),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C),the insulin sensitivity index(ISI),visceral fat mass over body weight ratio,and oral glucose tolerance test(OGTT) were assessed to confirm the establishment of MS with these models.The mRNA expression of ACE2 and ACE was determined by Real Time PCR and the distribution and the level of ACE2 protein in these tissues were determined by immunohistochemistry.HE staining was performed to observe the morphological changes.AngⅡwere evaluated with radioimmunoassay(RIA).Results:1.Levels of TG(1.18±0.19mmol/l vs 1.74±0.12mmol/l,P=0.000),TC (1.44±0.13mmol/l vs 2.04±0.18mmol/l,P=0.000),LDL-C(0.39±0.09mmol/l vs 0.89±0.12mmol/l,P=0.000),visceral fatmass over body weight ratio(0.0373±0.0019 vs 0.0442±0.0014,P=0.000) and BP(109.34±5.02mmHg vs 144.47±3.26 mmHg,P=0.000) were found to be markedly increased in the MS group compared with control group.Furthermore,a statistically significant reductions in amounts of HDL-C (0.75±0.12mmol/l vs 0.43±0.10mmol/l,P=0.000 ) and ISI(-4.48±0.07 vs -5.26±0.16,P=0.000)were observed in the MS group compared with the control group.OGTT abnormity was much obvious severe than that in the MS group(8.26±0.56mmol/l vs 9.22±0.59mmol/l,P=0.017).2.The expressions of ACE2 mRNA in the heart(0.972±0.126 vs 0.549±0.118,P=0.000),aortic endothelial(16.712±0.464 vs 8.527±0.279, P=0.000),lung(31.111±0.24 vs 12.452±0.111,P=0.000),kidney(37.477±0.268 vs 15.639±0.152,P=0.000),testis(4.854±0.049 vs 1.776±0.147,P=0.000)and brain (24.226±0.245 vs 4.823±0.15,P=0.000) were found to be significantly decreased in the MS rats compared with those of the control group.ACE2 mRNA in liver and pancreas was not found,ACE2 was expressed differently in various tissues of the rats with metabolic syndrome(0.972±0.126 vs 16.712±0.464 vs 31.111±0.24 vs 37.477±0.268 vs 4.854±0.049 vs 24.226±0.245,P=0.000,P=0.000,P=0.000,P=0.000, P=0.000,P=0.000).3.Compared with the control group,ACE mRNA in various tissues of MS group was increased statistically(heart:0.998±0.1 vs 3.156±0.103,aortic endothelial:2.139±0.117 vs 6.279±0.115,lung:2.645±0.105 vs 3.351±0.06,lever: 0.678±0.13 vs 1.171±0.119,kidney:8.777±0.102 vs 15.789±0.107,testis:6.322±0.105 vs 10.319±0.103,brain:3±0.112 vs 4.14±0.106,P=0.000,P=0.000,P=0.000, P=0.000,P=0.000,P=0.000,P=0.000),ACE mRNA in pancreas was not found.4.The protein content of ACE2 was found to be lower in MS group compared with that in control group(heart:0.3454±0.0244 vs 0.1823±0.0141,lung:0.3126±0.0391 vs 0.1784±0.0186,kidney:0.4133±0.0446 vs 0.1808±0.0195,testis:0.4538±0.0359 vs 0.1843±0.0186,P=0.001,P=0.000,P=0.000,P=0.001).5.The level of AngⅡof various tissue was found to be higher in MS group compared with that in control group(heart: 8.43±0.99 pg/mg vs 13.3±1.29 pg/mg,P=0.000,aortic:9.94±1.66 pg/mg vs 15.5±1.33 pg/mg,P=0.000,lung:7.52±1.12 pg/mg vs 10.62±1.25 pg/mg,P=0.000,liver: 5.46±1.02 pg/mg vs 8.19±1.06 pg/mg,P=0.000,pancreas:8.47±0.99 pg/mg vs 11.47±1.15 pg/mg,P=0.000,kidney:13.38±1.38 pg/mg vs 20.53±1.87 pg/mg,P=0.000, testis:7.15±1.01 pg/mg vs 10.23±1.24 pg/mg,P=0.000,brain:6.42±0.94 pg/mg vs 7.76±1.29 pg/mg,P=0.016) 6.HE staining showed pathological changes in heart and kidney of MS rat.7.There were some correlations among the ACE2,AngⅡwith other metabolic indexes(P<0.05).Conclusion:ACE2 mRNA in heart,aortic endothelial,lung,kidney,testis and brain were significantly decreased in the rats with MS.HE staining showed pathological changes in heart and kidney of MS rat.ACE 2 has a good correlation with ACE,AngⅡand metabolic indexes.These results are helpful to better understanding and tracing the situation of the target organ damage in MS.