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Objective:To study the effect of Fushengong prescreption on the regulation-antagonism effect of angiotensin converting enzyme-angiotensin Ⅱ-angiotensin Ⅱ 1 receptor （ACE-AngⅡ-AT1R） axis and angiotensin converting enzyme 2-angiotensin （1-7）-Mas receptor［ACE2-Ang（1-7）-MASR］ axis of rats with chronic renal failure（CRF）， and to explore its mechanism of delaying the development of CRF. Method:The 65 male SD rats were randomly divided into normal group （<italic>n</italic>=10） and modeling group （<italic>n</italic>=55）. The normal group was routinely reared， while the modeling group were administered by gavage with 0.25 g·kg<sup>-1</sup>d<sup>-1 </sup>adenine suspension for 28 days. After the model was successfully established， the survival model rats were randomly divided into model group， benazepril group（0.01 g·kg<sup>-1</sup>·d<sup>-1</sup>）and low，medium and high dose of Fushengong prescreption groups （4，8，16 g·kg<sup>-1</sup>·d<sup>-1</sup>）. The normal group and model group were administered the same volume of normal saline by gavage， lasted for 28 days. After the experiment， systolic blood pressure （SBP） and diastolic blood pressure （DBP） of caudal artery were measured， and 24-hour urine was collected to determine 24-hour urine protein （24 h U-pro）. The content of serum creatinine（SCr） and blood urea nitrogen （BUN） in the serum were measured， the histological morphology was observed by hematoxylin eosin（HE）staining， and the degree of renal interstitial fibrosis was observed by Masson staining. Enzyme linked immunosorbent assay （ELISA） was used to determine the contents of AngⅡ， Ang （1-7） and Cystatin C （CysC） in serum and renal homogenate. The protein level of ACE， ACE2， AT1R and MASR were detected by Western blot. The expression of ACE and ACE2 protein in renal tissues were detected by immunohistochemistry. Result:Compared with normal group， the expression levels of SCr， BUN and CysC in model group were significantly increased（<italic>P</italic><0.05）， the content of AngⅡ in serum and kidney tissues were significantly increased， the content of Ang （1-7） were significantly decreased（<italic>P</italic><0.05）， the expression of ACE and AT1R protein in renal tissues were significantly increased（<italic>P</italic><0.05）， and the expression of ACE2 and MASR protein were significantly decreased（<italic>P</italic><0.05）. Compared with model group and benazepril group， after the intervention with Fushengong prescreption， the serum SCr，BUN and CysC decreased（<italic>P</italic><0.05），the content of AngⅡ in serum and kidney tissues decreased significantly，Ang（1-7） increased significantly（<italic>P</italic><0.05）， the expression of ACE and AT1R protein in renal tissues decreased significantly（<italic>P</italic><0.05）， ACE2 and MASR protein increased significantly（<italic>P</italic><0.05）. The high-dose Fushengong prescreption has the best effect. The high， medium and low-dose effects of Fushengong prescreption were dose-dependent. Conclusion:Fushengong prescreption improved renal function and pathological change of kidney in adenine-induced rats with chronic renal failure. The mechanism may be related to the inhibition of ACE-AngⅡ-AT1R axis and promotion of ACE2-Ang（1-7）-MASR axis ，which leads to the delaying of the progression of chronic renal failure.
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To isolate the anti-angiotensin converting enzyme (ACE) constituents from Trichosanthis Pericarpium based on bioactivity-guided separation. Trichosanthis Pericarpium was extracted with boiling water and precipitated by ethanol, then its supernatant was collected and dialyzed. The retentate of the fractions above 1 000 was lyophilized to obtain GLP, which was then successively separated by DEAE Sepharose fast flow anion-exchange and Superdex-75 gel permeation chromatographic steps to achieve GLP-1-1. A combination of HPGPC, monosaccharide compositions determination and ACE inhibitory activity studies was performed to investigate the structure and bioactivity. The results showed that an anti-angiotensin converting enzyme oligosaccharide, GLP-1-1, was obtained from Trichosanthis Pericarpium based on activity tracking, whose average molecular weight was estimated to 1 367; mainly composed of arabinose, mannose, and glucose at a ratio of 0.2∶4.3∶10.0. GLP-1-1 showed potent anti-angiotensin converting enzyme effect with the IC₅₀of (113.4±8.6) mg•L⁻¹. In this study, an oligosaccharide with anti-angiotensin converting enzyme effect was isolated from Trichosanthis Pericarpium, which could lay the foundation for the substance basis study of Trichosanthis Pericarpium.
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Introducción: la preeclampsia constituye una causa importante de morbimortalidad materna y perinatal en el mundo. Su etiopatogenia es aún un enigma; sin embargo, los avances en genómica y proteómica prometen la identificación temprana de la enfermedad o del riesgo de padecerla. Objetivo: hacer una reflexión sobre los avances más promisorios de la genómica y proteómica, en el tamizaje y/o predicción de la preeclampsia. Conclusiones: dos polimorfismos funcionales, uno en el gen ACE (I/D) y otro en el gen COMT (Val158Met), poseen los resultados más promisorios para cumplir con el objetivo de identificar genéticamente a las mujeres con mayor riesgo de desarrollar preeclampsia durante un embarazo. Por su parte, la proteómica ha identificado a la SERPINA-1 como un biomarcador útil para detectar en la orina de las embarazadas que estén desarrollando la preeclampsia, con al menos 10 semanas de antelación a las manifestaciones clínicas de la misma y la necesidad de finalizar el embarazo. En conjunto, estos avances llevados a la práctica clínica podrían reducir el impacto de esta patología en la salud materna.
Introduction: preeclampsia is an important cause of maternal and perinatal morbi-mortality throughout the world. Its etiopathogeny still remains an enigma; however, the advances made in genomics and proteomics promise early identification of the disease or the risk of suffering from it. Objective: thoughts on the most promising advances in genomics and proteomics regarding the pressing goal of early detection and/or prediction of preeclampsia risk. Conclusions: two functional polymorphisms, one on the ACE gene (I/D) and another one in the COMT gene (Val158Met) are the most promising results of genomics for identifying women at genetically higher risk of developing preeclampsia during pregnancy. Proteomics has identified SERPINA-1 as a useful biomarker for detecting preeclampsia in the urine of pregnant women at least 10 weeks before clinical manifestations as well as the need for early termination of pregnancy. Such recent progress in genomics and proteomics adapted to clinical practice might reduce the impact of this disease on maternal health.
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Humans , Female , Adult , Genomics , Maternal Welfare , Pre-Eclampsia , Pregnancy , ProteomicsABSTRACT
The Angiotensin converting enzyme (ACE) is a dipeptidyl carboxypeptidase and plays an important role in the regulation of blood pressure. Several potent inhibitors of this enzyme have been reported to be active antihypertensive agents. Sulfhydryl (SH) group containing ACE inhibitors used as a antihypertensive agents. Reduced glutathione (GSH) as antioxidant play an important role in reducing the blood pressure. Several recent studies have shown that reduced glutathione enhance nitric oxide pathway and increases the bioavailability of nitric oxide resulting in vasodilatation. In this study reduced glutathione and oxidized glutathione (GS-SG) were investigated for inhibition against ACE using Hip-His-Leu (HHL) as substrate. The inhibition of ACE by different concentrations of reduced glutathione was much more than that of oxidized glutathione. The inhibition of ACE by reduced glutathione ranges from 12.5% to 60%. Oxidized glutathione shows less than 5% of inhibition. This study shows that apart from the antioxidant role, reduced glutathione inhibits ACE activity which plays a crucial role in the regulation of blood pressure.
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OBJECTIVES: Angiotensin-converting enzyme (ACE) gene polymorphism has been reported to be associated with depression and therapeutic outcome in depression. The purpose of this study was to determine whether ACE gene polymorphism is associated with seasonal variation in mood and behavior in a young Korean college student sample. METHODS: 297 young Korean medical students were recruited in this study. All subjects were free of major medical and psychiatric problems. They were genotyped for the ACE gene polymorphism and evaluated the seasonal variation in mood and behavior by the Seasonality Pattern Assessment Questionnaire (SPAQ). RESULTS: Global Seasonality Score (GSS) of SPAQ between three genotypes were not different. However, comparison of the group that showed seasonality of mood and behavior during winter with the group that did not showed seasonality indicated significant difference in genotype distribution (chi-square=6.79, p=0.034). The D allele non-carrier (II genotype) frequency was significantly higher in winter seasonality group than non-seasonality group (chi-square=6.59, p=0.010; odds ratio [OR]=2.27, 95% confidence interval [CI] 1.20-4.28). CONCLUSION: These results suggest that the ACE gene polymorphism is related to winter-type seasonality in a Korean population.
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Humans , Alleles , Depression , Genotype , Odds Ratio , Surveys and Questionnaires , Seasons , Students, MedicalABSTRACT
BACKGROUND: The aim of this study was to investigate the association between apo E and ACE genetic polymorphism and diabetic nephropathy. METHODS: One hundred eighteen patients with type 2 diabetes who had a duration of diabetes longer than 8 years were divided into the three apo E groups (E2, E3, E4) and three ACE groups (II, ID, DD). Plasma levels of lipids were measured. The frequency of diabetic nephropathy and clinical and biochemical characteristics were compared among the Apo E and ACE genotype groups. RESULTS: The frequency of overt nephropathy was significantly greater in apo E2 patients with diabetes (46.7%) than apo E3 (16.7%) or apo E4 patients (10.5%). Logistical regression analysis showed that odds ratio of apo E2 and apo E4 genotypes for the presence of overt nephropathy were 4.779 (p<0.01) and 0.643 (p=0.583), respectively. Plasma TG levels were significantly greater in apo E2 patients. This study did not show an association between ACE gene polymorphism and diabetic nephropathy, and no interaction between Apo E and ACE gene polymorphism. CONCLUSION: Apo E2 is a prognostic risk factor for diabetic nephropathy in Korean type 2 diabetes. TG may have an important role of diabetic nephropathy. There were not synergistic effect between Apo E and ACE gene polymorphism in diabetic nephropathy.
Subject(s)
Humans , Apolipoprotein E2 , Apolipoprotein E3 , Apolipoprotein E4 , Apolipoproteins E , Apolipoproteins , Diabetic Nephropathies , Genotype , Odds Ratio , Plasma , Polymorphism, Genetic , Risk FactorsABSTRACT
PURPOSE: Studies concerning the relationship between gene polymorphisms and potentially implicated cardiovascular disease have produced conflicting findings, in part due to differences in ethnic background between populations. These led us to evaluate the impact of polymorphisms in the ACE and E-selectin genes on peripheral artery atherosclerosis in a Korean population. METHODS: We studied 92 male patients (median age: 65.9, range: 48~82) with severe peripheral atherosclerosis documented by angiography and ABI (ankle brachial index). The control group comprised 290 healthy persons (male 216, female 64, median age 61.3, range 20~90) without symptoms for peripheral vascular disease. The blood samples were stored at -20oC until DNA was ready to be extracted. The inorganic procedure for DNA extraction was based on the method described by Miller et al. The ACE and E-selectin polymorphisms were detected by polymerase chain reaction (PCR) amplification. RESULTS: The distribution of ACE genotypes of the patient group was as follows: II, 34 (37.0%); ID, 46 (50.0%); and DD, 12 (13.0%). It was not significantly different from that of the control subjects: II, 104 (37.1%); ID, 133 (47.6%); and DD, 43 (15.3%) (P=0.80). The allele frequencies of the patient group were as follows: I, 114 (62.0%); and D, 70 (38.0%). It was not significantly different from that of the control subjects: I, 341 (60.9%); and D, 219 (39.1%) (P= 0.80). The frequencies of E-selectin genotypes in the patient group were as follows: Ser/Ser 85 (93.4%); Ser/Arg, 6 (6.6); and Arg/Arg, 0 (0%). It was not significantly different from that of the control subjects: Ser/Ser, 262 (93.6%); Ser/Arg, 18 (6.4%); and Arg/Arg, 0 (0%) (P=0.95). In addition, the allele frequencies of the patient group were as follows: Ser, 176 (96.7%); and Arg, 6 (3.3%). It was not significantly different from that of the control subjects: Ser, 542 (96.8%); and Arg 18 (3.2%) (P=0.95). CONCLUSION: The I/D polymorphism of the ACE gene and E-selectin S128R polymorphism were not significantly different between the atherosclerotic patient group and the normal control group in Koreans.
Subject(s)
Female , Humans , Male , Angiography , Angiotensins , Arteries , Atherosclerosis , Cardiovascular Diseases , DNA , E-Selectin , Gene Frequency , Genotype , Peptidyl-Dipeptidase A , Peripheral Vascular Diseases , Polymerase Chain Reaction , Polymorphism, GeneticABSTRACT
@#ObjectiveTo explore the association between angiotensin converting enzyme (ACE) gene insertion/deletion(I/D) polymorphism and cerebral infarction among Chinese people. MethodsThe ACE gene polymorphism was determined by PCR-RFLP in 242 patients with cerebral infarction and 283 controls. Multiple logistic regression was performed to explore the risk factors for cerebral infarction. ResultsAfter adjusting age, gender, alcohol drinking, smoking, education,history of diabetes mellitus and the primary hypertension, there was no significant association between ACE I/D polymorphism and cerebral infarction, either was hypertension and diabetes mellitus. The primary hypertension significanlly increased risk of cerebral infarction (OR=7.28,P =0.000). Both ACE ID/DD genotype and the primary hypertension showed a significant gene-environment interaction(r=1.62,OR=7.29), something as super multiplicative type 2 interaction. ConclusionAlthough ACE gene polymorphism is not risk factors of cerebral infarction, but ID/DD genotype had shown significant gene-environment interaction with primary hypertension in occurrence of cerebral infarcion.
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Objective To study the single and combined-enzymic hydrolysis conditions of Oreochromis niloticus skin collagen.Methods Based on the inhibitory activities of six kinds of single enzymic hydrolysates to angiotensin converting enzyme(ACE),bromelain and alcalase(2.4L) were selected as combined-enzyme.The optimal hydrolytic conditions of the skin collagen with the two enzymes were determined by orthogonal test L_(16)(4~(5)).Results and Conclusion The results showed that the optimal hydrolytic conditions of bromelain and alcalase 2.4L were temperature 45℃,pH4.5,E/S 4000U?g~(-1),time 4h,concentration of substrate 6%;and temperature 55℃,pH7.5,E/S 6000U?g~(-1),time 2h,concentration of substrate 4%,respectively.Furthermore,hydrolytic effect would be better when using bromelain in advance,followed by alcalase 2.4L.The hydrolytic degree of the hydrolysates prepared under the provided technology was 30.43%,the ACE inhibitory rate would be as high as(68.65%) in vitro.
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Objective To study changes in ACE, LDH and AKP in BALF and blood after rapid decompression in rabbits. Methods Thirty healthy New-Zealand rabbits were randomly divided into low decompression group and rapid decompression group. The respective activity of ACE, LDH and AKP in BALF and blood of rabbits was measured. Results Various degrees of increase in activity of ACE, LDH and AKP in BALF were observed after rapid decompression. Conclusion The simultaneous enhancement of activity of these enzymes suggest that there was injury to the lung consistent with the degree of injury after rapid decompression.
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An Insertion/deletion polymorphism in angiotensin converting enzyme gene has been considered the important regulator of ACE activity in plasma and tissue. The deletion allele of this gene is associated with higher ACE activity, which ultimately increased angiotensin II formation. It is possible that alteration of ACE polymorphism might be contribute to development of end stage renal disease and cardiovascular disease where RAS system is implicated in disease process. This study determined the distribution of ACE genotype in 122 end stage renal disease patients and in a group of 101 healthy controls. Also we evaluated the difference of allele frequency in the hemodialysis patients with or without cardiovascular disease. ACE genotype was determined by polymerase chain reaction technique from the PBMC leukocytes of the patients. The results were as follows; 1)Patients population consisted of 122 hemodialysis patients and male to female ratio was 66:56, mean age was 54.3+/-12.8 years old. Mean duration of dialysis treatment was 52.5+/-37.5 months and the underlying disease of ESRD were diabetic nephropathy in 78 cases, chronic glomerulonephritis in 29 cases, hypertension in 8 cases, other disease in 7 cases. 2)In the contol patients, male to female ratio was 52:49, mean age was 46.1+/-15.1 years old. The age and sex distribution between ESRD and control group was not significantly different. 3)Of the total hemodialysis patients, 26.2% showed the II genotype, 35.2% of ID genotype and 38.6% of DD genotype. In the contol group, the frequency of each genotype was 20.8% of II, 55.4% of ID and 23.8% of DD genotype. The frequency of DD genotype was significantly higher in ESRD group than control group(p<0.05). 4)In the ESRD patients, 72 patients(59%) had the LVH and 23 patients(18%) had the ischemic heart disease. The genotype distribution in ESRD patients according to the presence of LVH or ischemic heart disease did not show any significant difference. The frequency of each genotype in the patients with LVH showed 22.2%(II), 43.1%(ID), 34.7%(DD), and 32.8%(II), 37.5%(ID), 29.7%(DD) in the patients without LV et al.:Angiotensin Converting Enzyme Polymorphism in Patients with End Stage Renal Disease- H. In the aspect of ischemic heart disease, the frequency of ACE genotype was 27.3%(II), 45.5% (ID), 27.3%(DD) in the group of ischemic heart disease, compared with the ditribution of 31.5 %(II), 40%(ID), 32.6%(DD) in the patients without ischemic heart disease. From the above results, it was concluded that insertion/deletion polymorphism in angiotensin converting enzyme gene, especially DD genotype, may be important in the pathogenesis of progression to end stage renal disease. There was no significant difference in I/D polymorphism according to the presence or absence of cardiovascular complications
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Female , Humans , Male , Alleles , Angiotensin II , Angiotensins , Cardiovascular Diseases , Diabetic Nephropathies , Dialysis , Gene Frequency , Genotype , Glomerulonephritis , Hypertension , Kidney Failure, Chronic , Leukocytes , Myocardial Ischemia , Peptidyl-Dipeptidase A , Plasma , Polymerase Chain Reaction , Renal Dialysis , Sex DistributionABSTRACT
OBJECTIVE: Diabetic nephropathy is an important cause of end-stage renal disease and associated with morbidity and mortality of the patients with diabetes mellitus. It has been reported that the genetic susceptibility may be an important factor in the development of nephropathy in diabetic patients, but the genes responsible for the predisposition to diabetic nephropathy are not known. The genes of the renin-angiotensin systems are plausible candidate genes and the genetic polymorphism of angiotensin-converting enzyme(ACE) gene has been extensively studied for its possible role. Recently, the association of the ACE gene polymorphism with nephropathy as well as myocardial infartion was reported in diabetic patients. To elucidate the contribution of ACE gene polymorphism to the initiation and progression of diabetic nephropathy, we typed the alleles of the ACE gene in 139 patients with non-insulin dependent diabetes mellitus (NIDDM). METHODS: After the extraction of genomic DNA from peripheral blood leukocytes, PCRs were performed using the flanking and insertion specific primers, respectively. The PCR products were electrophoresed in 1.5% agarose gels, and DNA was visualized directly with ethidium bromide staining. RESULTS: Subjects were consisted of 139 patients with diabetes mellitus and male to female ratio was 63:76, mean age 55.8+/-12.0 years, mean duration of diabetes 9.5+/-7.8 years. ACE genotypes in whole population were 37.4% DD genotype, 51.1% ID genotype and 11.5% II genotype. The ACE genotype distributions, age, sex, blood pressure and body mass index were not different in diabetic subjects with or without nephropathy. No significant differences on the clinical parameters such as age, sex, blood pressure, body mass index, duration of diabetes, incidence of hypertension, cardiovascular complication, diabetic neuropathy and retinopathy, serum creatinine and 24hour albumin excretion were noted according to the ACE genotypes. Forty-six patients with NIDDM were followed over 3 years. The mean follow-up duration was 6.4+/-2.7 years, mean age was 54.4+/-10.2 years, and mean duration of diabetes was 14.7+/-6.1 years. ACE genotypes were 36.9% DD genotype, 52.2% ID genotype and 10.9% II genotype. The ACE genotype distributions were not different in the patients among DD, II or II genotypes. There were also no significant differences in terms of age, sex, duration of diabetes, blood pressure, body mass index, prevalence of hypertension, cardiovascular complication, diabetic neuropathy and diabetic retinopathy. But the rate of decline of creatinine clearance(deltacreatinine clearance, ml/min/year) was higher in DD genotype than ID or II genotypes(3.3+/-7.2 vs 2.8+/-6.2 vs 2.7+/-9.8), and the rate of change of 24-hour protein excretion(deltaurinary protein excretion, mg/24hours/year) was higher in DD genotype than ID or II genotypes(89.3+/-220.0 vs 74.1+/-156.8 vs 70.9+/-546.3). But they did not reach to statistical significance. CONCLUSION: We found that insertion/deletion polymorphism of ACE gene is not implicated in the initiation of diabetic nephropathy of Korean NIDDM patients, but also found the possibility that progression of diabetic nephropathy may be associated with it. We need large scaled prospective follow-up studies on the effects of ACE polymorphism in the progression of diabetic nephropathy.
Subject(s)
Female , Humans , Male , Age Distribution , Alleles , Angiotensins , Blood Pressure , Body Mass Index , Creatinine , Diabetes Mellitus , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Diabetic Neuropathies , Diabetic Retinopathy , DNA , Ethidium , Follow-Up Studies , Gels , Genetic Predisposition to Disease , Genotype , Hypertension , Incidence , Kidney Failure, Chronic , Leukocytes , Mortality , Polymerase Chain Reaction , Polymorphism, Genetic , Prevalence , Renal Insufficiency , Renin-Angiotensin System , SepharoseABSTRACT
BACKGROUND: It has been suggested that all components of the renin-angiotensin-aldosterone system (RAAS) are present in the vascular wall and that the vascular RAAS modulates vascular tone and vascular hypertrophy. One of the catalytic step in the RAAS cascade is the local conversion of angiotensin I to angiotensin II (Ang II) by angiotensin converting enzyme (ACE). One of the major sources of ACE in the vasculature is vascular smooth muscle cells (VSMC). Here, we provide insight into the intrinsic mechanisms by which the components of RAAS regulate gene expression of ACE in cultured smooth muscle cells of the rat and we also investigated the effects of cytokines on ACE mRNA. METHODS: RNA was extracted from the primary cultured VSMCs. We analyzed the expression levels of ACE by competitive reverse transcription-PCR using recombinant RNA as an internal standard. RESULTS: 1) ACE mRNA level was increased markedly by aldosterone in a dose- and time-dependent manner, indicating that there exists positive feedback mechanism within RAAS. 2) The induction of ACE mRNA by aldosterone was inhibited by spironolactone. 3) Aldosterone-stimulated expression of ACE was also inhibited by Ang II, which shows that Ang II acts as a negative regulator of the expression of ACE in RAAS cascade. 4) Interleukin-1beta or TNF-alpha did not induce ACE mRNA expression. 5) However, mixture of interleukin-1betaand TNF-alpha(CytoMix) significantly increased the expression of ACE. It was also shown that CytoMix increased aldosterone-stimulated ACE mRNA expression in an additative manner. CONCLUSION: These results indicate that the expression of ACE in smooth muscle cells is modulated by the components of RAAS and cytokines. The intrinsic positive and negative feedback controls of RAAS would play an important role in the pathogenesis of vascular diseases.