Serum Angiotensin I-converting Enzyme Research Articles

The Relationship between Tumor Development and Sarcoidosis in Aspects of Carcinogenesis before and after the Onset of Sarcoidosis.

Background and Objectives: It is still unclear whether sarcoidosis is likely to be associated with tumors. In addition, the use of an immune checkpoint inhibitor has been reported to initiate the onset of sarcoidosis. We retrospectively analyzed tumor development before and after the diagnosis of sarcoidosis and examined the impact of having a history of tumors on the activity or the severity of sarcoidosis. Materials and Methods: We recruited 312 consecutive cases of sarcoidosis and analyzed the tumor development before and after the onset of sarcoidosis. Results: Among them, 25 cases were diagnosed with malignant tumor after diagnosis of sarcoidosis. In the analysis of the tumor-development group after diagnosis of sarcoidosis, both serum angiotensin I-converting enzyme and mediastinal lymph node size were significantly reduced at the time of malignant tumor diagnosis compared to at the onset of sarcoidosis, indicating that the decreasing activity of sarcoidosis may be partly associated with tumor development. Furthermore, we examined 34 cases having tumor history before the onset of sarcoidosis and analyzed the effect of tumor history on the severity of sarcoidosis. Cases with a malignant tumor in the past were older and had less complicated organs of sarcoidosis than cases without malignant tumors in the past. Oral corticosteroid therapy was administrated more frequently in cases without malignant tumors in the past, indicating that the history of a malignant tumor may influence the severity of sarcoidosis. Conclusion: These results indicate that tumor development may be partly associated with the activity or severity of sarcoidosis.

Novel ACE mutations mimicking sarcoidosis by increasing blood ACE levels

An elevated blood angiotensin I-converting enzyme (ACE) supports diagnosis of sarcoidosis and Gaucher disease. However, some ACE mutations increase ACE shedding, and patients with these mutations are therefore at risk of being incorrectly diagnosed with sarcoidosis because of elevated serum ACE levels. We applied a novel approach called "ACE phenotyping" to identify possible ACE mutations in 3 pulmonary clinic patients that had suspected sarcoidosis based on elevated blood ACE levels. Conformational fingerprinting of ACE indicated that these mutations may be localized in the stalk region of the protein and these were confirmed by whole exome sequencing. Index patient 1 (IP1) had a mutation (P1199L) that had been previously identified, while the other 2 patients had novel ACE mutations. IP2 had 2 mutations, T887M and N1196K (eliminating a putative glycosylation site), while IP3 had a stop codon mutation Q1124X (eliminating the transmembrane anchor). We also performed a comprehensive analysis of the existing database of all ACE mutations to estimate the proportion of mutations increasing ACE shedding. The frequency of ACE mutations resulting in increased blood ACE levels may be much higher than previously estimated. ACE phenotyping, together with whole exome sequencing, is a diagnostic approach that could prevent unnecessary invasive and/or costly diagnostic procedures, or potentially harmful treatment for patients misdiagnosed on the basis of elevated blood ACE levels.

Tissue ACE phenotyping in lung cancer.

BackgroundPulmonary vascular endothelium is the main metabolic site for Angiotensin I-Converting Enzyme (ACE)-mediated degradation of several biologically-active peptides (angiotensin I, bradykinin, hemo-regulatory peptide Ac-SDKP). Primary lung cancer growth and lung cancer metastases decrease lung vascularity reflected by dramatic decreases in both lung and serum ACE activity. We performed precise ACE phenotyping in tissues from subjects with lung cancer.MethodologyACE phenotyping included: 1) ACE immunohistochemistry with specific and well-characterized monoclonal antibodies (mAbs) to ACE; 2) ACE activity measurement with two ACE substrates (HHL, ZPHL); 3) calculation of ACE substrates hydrolysis ratio (ZPHL/HHL ratio); 4) the pattern of mAbs binding to 17 different ACE epitopes to detect changes in ACE conformation induced by tumor growth (conformational ACE fingerprint).ResultsACE immunostaining was dramatically decreased in lung cancer tissues confirmed by a 3-fold decrease in ACE activity. The conformational fingerprint of ACE from tumor lung tissues differed from normal lung (6/17 mAbs) and reflected primarily higher ACE sialylation. The increase in ZPHL/HHL ratio in lung cancer tissues was consistent with greater conformational changes of ACE. Limited analysis of the conformational ACE fingerprint in normal lung tissue and lung cancer tissue form the same patient suggested a remote effect of tumor tissue on ACE conformation and/or on “field cancerization” in a morphologically-normal lung tissues.Conclusions/SignificanceLocal conformation of ACE is significantly altered in tumor lung tissues and may be detected by conformational fingerprinting of human ACE.

The Relationship of Angiotensin I-Converting Enzyme Genotype to Liver Fibrogenesis in Non-Alcoholic Steatohepatitis

AbstractBackground: Multiple genetic and environmental factors may lead to fibrogenesis in patients with Non-alcoholic fatty liver (NAFL). Many studies investigated the relation of angiotensin I-converting enzyme (ACE) genotyping to liver fibrosis in chronic liver disease; and the results are contradic-tory.Aim of Study: In the current study, ACE genotype was assessed in NAFLD patients to show its possible association with development liver fibrosis.Subjects and Methods: The study included 162 patients of NAFLD disease, 49 (30.25%) patients with mild fibrosis, 65 (40.12%) with moderate fibrosis and 48 (29.63%) with severe fibrosis in addition to 138 volunteers was enrolled as a healthy controls. All patients and controls were investigated to serum glucose and fasting insulin level and HOMA-IR was calculated. Liver function tests, both serum ACE and trans-forming growth factor-beta (TGF-b) were done. ACE geno-typing [insertion/deletion (I/D)] was done by PCR.Results: Fasting glucose and insulin, HOMA-IR, AST, ALT and GGT were significantly higher in NAFLD patients than healthy controls. The homozygous frequency I/I and D/D or D/I of ACE were not significantly different between NAFLD patients and controls. The D/D genotype was associated significantly with the severity of liver fibrosis, D/I polymor-phism with moderate fibrosis and I/I genotype with mild fibrosis. The higher D allele frequency was associated with severe fibrosis, while I allele was frequent in mild fibrosis. The HOMA-IR, ALT, serum ACE and TGF-b were increased significantly in the patients carrying D/D homozygous gene more than those carrying homozygous I/I or D/I polymorphism. The serum ACE and TGF-b were significantly higher in NAFLD patients compared to control and the most higher levels was reported in cases with severe liver fibrosis than moderate and mild liver fibrosis.Conclusion: ACE (D/D) genotype was closely associated with liver fibrosis severity and ACE (I/D) polymorphism was observed in moderate stage of fibrosis. The allele D is seems to be a risk factor for liver fibrosis development than allele I. The knowledge of the ACE genotypes in NAFLD patients may be important for treatment decision in those patients and beneficial in the follow-up of the disease progression.

Antihypertensive Effect in Vivo of QAGLSPVR and Its Transepithelial Transport Through the Caco-2 Cell Monolayer.

The peptide QAGLSPVR, which features high angiotensin-I-converting enzyme (ACE) inhibitory activity, was identified in our previous study. In this study, the in vivo antihypertensive effect of QAGLSPVR was evaluated. Results showed that QAGLSPVR exerts a clear antihypertensive effect on spontaneously hypertensive rats (SHRs), and the systolic and diastolic blood pressures of the rats remarkably decreased by 41.86 and 40.40 mm Hg, respectively, 3 h after peptide administration. The serum ACE activities of SHRs were determined at different times, and QAGLSPVR was found to decrease ACE activities in serum; specifically, minimal ACE activity was found 3 h after administration. QAGLSPVR could be completely absorbed by the Caco-2 cell monolayer, and its transport percentage was 3.5% after 2 h. The transport route results of QAGLSPVR showed that Gly-Sar and wortmannin exert minimal effects on the transport percentage of the peptide (p> 0.05), thus indicating that QAGLSPVR transport through the Caco-2 cell monolayer is not mediated by peptide transporter 1 or transcytosis. By contrast, cytochalasin D significantly increased QAGLSPVR transport (p< 0.05); thus, QAGLSPVR may be transported through the Caco-2 cell monolayer via the paracellular pathway.

Protein Malnutrition Alters Tryptophan and Angiotensin-Converting Enzyme 2 Homeostasis and Adaptive Immune Responses in Human Rotavirus-Infected Gnotobiotic Pigs with Human Infant Fecal Microbiota Transplant.

Malnutrition leads to increased morbidity and is evident in almost half of all deaths in children under the age of 5 years. Mortality due to rotavirus diarrhea is common in developing countries where malnutrition is prevalent; however, the relationship between malnutrition and rotavirus infection remains unclear. In this study, gnotobiotic pigs transplanted with the fecal microbiota of a healthy 2-month-old infant were fed protein-sufficient or -deficient diets and infected with virulent human rotavirus (HRV). After human rotavirus infection, protein-deficient pigs had decreased human rotavirus antibody titers and total IgA concentrations, systemic T helper (CD3+ CD4+) and cytotoxic T (CD3+ CD8+) lymphocyte frequencies, and serum tryptophan and angiotensin I-converting enzyme 2. Additionally, deficient-diet pigs had impaired tryptophan catabolism postinfection compared with sufficient-diet pigs. Tryptophan supplementation was tested as an intervention in additional groups of fecal microbiota-transplanted, rotavirus-infected, sufficient- and deficient-diet pigs. Tryptophan supplementation increased the frequencies of regulatory (CD4+ or CD8+ CD25+ FoxP3+) T cells in pigs on both the sufficient and the deficient diets. These results suggest that a protein-deficient diet impairs activation of the adaptive immune response following HRV infection and alters tryptophan homeostasis.

Combinative effect of sardine peptides and quercetin alleviates hypertension through inhibition of angiotensin I converting enzyme activity and inflammation

Hypertension had relation to angiotensin I converting enzyme (ACE) activity and inflammation. In our previous research, sardine peptides (SP) with ACE inhibitory activity were prepared. However, the combinative effect of SP and quercetin (QC) on hypertension alleviation was still unknown. In the present study, the antihypertensive effect of SP and QC was discovered and the optimal proportion of SP and QC (v/v=8:2, with 20.00mg/mL of SP and 12.99μg/mL of QC for their original concentrations) was screened on ACE activity inhibition in vitro. And the in vivo experiment supported it by indicating that the mixture reduced the systolic blood pressure, heart, left ventricular and kidney weight and their corresponding indices, serum ACE activity, angiotensin-II (ANG-II) and tumor necrosis factor-α (TNF-α) (in high dose) concentration in SHR rats. Besides, the mixture also lowers NO, TNF-α andinterleukin-6 (IL-6) concentration significantly in vitro. Hence, the combinative effect of SP and QC in optimal proportion had stronger inhibition on ACE activity than SP or QC alone, and could alleviate hypertension through inhibition of ACE activity and inflammation.

Correlations between ACE single nucleotide polymorphisms and prognosis of patients with septic shock.

The aim of the present study is to investigate association between septic shock (SS) and angiotensin I-converting enzyme (ACE) single nucleotide polymorphisms (SNPs). From October 2009 to December 2016, 238 SS patients and 242 healthy individuals were selected for our study. ACE activity was detected, ACE rs4291 and rs4646994 polymorphisms were detected using PCR-restriction fragment length polymorphism (PCR-RFLP). The Kaplan–Meier survival curve was employed to evaluate the association between ACE SNPs and patients’ survival and univariate and multivariate analyses to estimate risk factors for SS. ACE activity in the case group was increased in comparison with the control group. Allele and genotype frequencies of rs4291 and rs4646994 were different between the case and control groups. The TT genotype frequency of the rs4291 polymorphisms and the DD genotype of the rs4646994 polymorphisms of the case group were higher than those in the control group. The AT and TT genotypes indicated a significant elevation of ACE activity than the AA genotype, while a significant decline was found in the DI and II genotypes in comparison with the DI genotype. Patients with TT or DD genotypes had increased fatality rate within 7 and 30 days when compared with those with non-TT or non-DD genotypes. Lower sepsis-related organ failure assessment (SOFA) scores, rs4291, serum ACE and rs4646994 were all considered as risky factors for SS patients. The study demonstrates that TT genotype of rs4291 or DD genotype of rs4646994 may be indicative of a higher risk of SS and a poorer prognosis in SS patients.

Angiotensin-I-Converting Enzyme Inhibitory Activities and In Vivo Antihypertensive Effects of Sardine Protein Hydrolysate.

In our previous study, an antihypertensive protein hydrolysate was prepared from sardine. This study aimed to investigate the composition of sardine protein hydrolysate (SPH) and it's in vivo antihypertensive effect. SPH was separated sequentially with ultrafiltration and size exclusion chromatography. Fractions with high angiotensin-I-converting enzyme (ACE) inhibitory activity were further analyzed with RP-HPLC and amino acids analysis. Then, SPH was individually oral administrated to spontaneously hypertensive rats (SHR) and normotensive wistar kyoto rats (WKY) for 4 wk. After treatment, the systolic blood pressure (SBP), organindex, oxidative status, serum ACE activity, and serum angiotensin-II (ANG-II) of all the rats were determined. According to the separation and analysis results, 3 main fractions with high ACE-inhibitory activity were obtained with different amino acids composition. The animal experiments results showed that SPH could significantly reduce SBP (P < 0.05 or P < 0.01) within 4 h after a single oral administration. After a chronic oral administration, a steady state of SBP in SHR rats was attained. The heart weight index and left ventricular weight index were significantly reduced (P < 0.05) in SPH-treated SHR rats. The malonyldialdehyde (MDA) levels in organs and serum, serum ACE activity, and serum ANG-II concentration in SPH-treated SHR rats were significantly lowered (P < 0.05 or P < 0.01) as compared to their controls. Meanwhile there was no significant effect (P > 0.05) on those parameters in WKY rats. These results indicate that SPH can decrease blood pressure in SHR rats and not in WKY rats.

Correlation of spleen metabolism assessed by 18F-FDG PET with serum interleukin-2 receptor levels and other biomarkers in patients with untreated sarcoidosis.

The objective of our study was to assess the possible relationship between splenic F-18-fluorodeoxyglucose (18F-FDG) uptake and other established biochemical markers of sarcoidosis activity. Thirty treatment-naive sarcoidosis patients were prospectively enrolled in this study. They underwent biochemical laboratory tests, including serum interleukin-2 receptor (sIL-2R), serum C-reactive protein, serum angiotensin-I converting enzyme, and 24-h urine calcium levels, and a whole-body combined 18F-FDG PET/computed tomography (PET/CT) scan as a part of an ongoing study at our institute. These biomarkers were statistically compared in these patients. A statistically significant linear dependence was detected between sIL-2R and log-transformed spleen-average standard uptake value (SUV avg) (R2=0.488, P<0.0001) and log-transformed spleen-maximum standard uptake value (SUV max) (R2=0.490, P<0.0001). sIL-2R levels and splenic size correlated linearly (Pearson's r=0.373, P=0.042). Multivariate linear regression analysis revealed that this correlation remained significant after age and sex adjustment (β=0.001, SE=0.001, P=0.024). No statistically significant associations were detected between (a) any two serum biomarkers or (b) between spleen-SUV measurements and any serum biomarker other than sIL-2R. Our analysis revealed an association between sIL-2R levels and spleen 18F-FDG uptake and size, whereas all other serum biomarkers were not significantly associated with each other or with PET 18F-FDG uptake. Our results suggest that splenic inflammation may be related to the systemic inflammatory response in sarcoidosis that may be associated with elevated sIL-2R levels.

Processed soymilk effectively ameliorates blood pressure elevation in spontaneously hypertensive rats

Processed soymilk (PSM) was produced from original soymilk by treatment with a commercially available proteinase to generate inhibitory peptides against the angiotensin I-converting enzyme (ACE). Furthermore, we investigated PSM's potential hypotensive effect on spontaneously hypertensive rats (SHR). Processed soymilk at doses of 0.167 and 0.583 ml/kg body weight after a single oral administration significantly decreased systolic blood pressure in SHR compared to control (non-processed soymilk). Repeated administration (3 weeks) of PSM at the same doses significantly reduced blood pressure elevation in SHR compared to control. After repeated PSM administration, its inhibitory activity against serum ACE was significantly higher compared to the control. Serum levels of the angiotensin II after PSM administration was significantly lower than control. Serum lipid profiles were similar between control and experimental (PSM) SHR. Thus, PSM ingestion may lower high blood pressure and ameliorate cardiovascular diseases related to hypertension without causing adverse side effects.

The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.

Angiotensin converting enzyme (ACE D/I) polymorphism and its relation to liver fibrosis progression in Egyptian patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV) infection is a global health problem in Egypt and causes different liver disease spectrum. Evidence indicates that angiotensin I converting enzyme (ACE) gene polymorphism may play a role in determining disease progression. We aimed to determine the association of ACE gene I/D polymorphism with ACE serum levels and to examine the association between different I/D genotypes with the severity of hepatic fibrosis in chronic HCV infected Egyptian patients. Thirty controls and 90 HCV infected patients participated in the study, patients were subgrouped by Ishak stage of fibrosis into subgroup IIa (n=30; fibrosis score 0–1), subgroup IIb (n=38; fibrosis score 2–3) and subgroup IIc (n=22; fibrosis score 4–6). DNA was multiplied by polymerase chain reaction (PCR). ACE genotype frequency in HCV infected patients was significantly different comparing to controls (X2=7.169, P=0.028). With non-significant difference in ACE D/I genotypes and allele frequencies among the patient subgroups (P>0.05),the frequency of the DD, DI and II genotypes in subgroup IIa, subgroup IIb and subgroup IIc were (53.3%, 36.6%, 10%), (44.7%, 44.7%, 10.5%) and (50%, 22.7%, 27%), respectively. The D and I allele frequency were (71.66%, 28.33%), (67.1%, 32.9%) and (61.36%, 38.63%), respectively. ACE serum levels were significantly increased in DD more than DI and II (t=2.56, 3.43, P<0.05), respectively, with non-significant association in sonographic findings, viral load and liver function test (LFT) parameters with the ACE genotypes. Serum ACE levels were significantly increased in all patient subgroups when compared to controls with a non significant difference of ACE levels between subgroup IIb and IIc. We concluded that the D/D genotype is associated with HCV infection but not associated with degree or the progression of hepatic fibrosis.

Serum angiotensin I-converting enzyme response to exercise; no differential effect of genotype

Angiotensin I-converting enzyme (ACE) plays a pivotal role in whole body fluid balance and the degradation of bradykinin. A common allelic variant with a 287 base pair insert has been...

Serum Angiotensin I-Converting Enzyme Levels and the Therapeutic Effects of Octreotide in Esophageal Variceal Hemorrhage

IntroductionThe aim of this study is to investigate the relationship between serum angiotensin I-converting enzyme (ACE) levels and therapeutic effects of octreotide in the treatment of esophageal variceal hemorrhage (EVH) as a result of liver cirrhosis. MethodsSerum ACE levels were measured by ultraviolet light colorimetric analysis in 80 cases of liver cirrhosis with EVH before and after the treatment of various doses of octreotide (25 and 50 μg/hr treatment in 40 cases, respectively), which were compared with 20 healthy controls. ResultsBetween the octreotide treatment groups, there were no significant differences in the Child-Pugh score, the endoscopic severity of esophageal varices and ACE levels before octreotide treatment. Pretreatment levels of serum ACE were markedly higher in patients with EVH compared with healthy controls (P < 0.001). Serum ACE levels were significantly higher before octreotide treatment than 72hours after treatment in patients with EVH. Serum ACE after octreotide treatment declined more evidently in the 50 μg/hr than in the 25 μg/hr treatment group. The hemostatic rate within 6hours after octreotide treatment was significantly higher in the 50 μg/hr than in the 25 μg/hr treatment group. The rebleeding rate within 72hours after octreotide treatment was markedly lower in the 50 μg/hr than in the 25 μg/hr treatment group. ConclusionsOctreotide treatment in patients with EVH can result in decreased serum ACE levels, which correlated with the dose of octreotide. The decline in serum ACE levels may be involved in the mechanisms by which octreotide lowers portal vein pressure in EVH treatment.

251 Renin-angiotensin-aldosterone system polymorphisms: a role or a hole in occurrence and long-term prognosis of acute myocardial infarction at Tunisian older people

Myocardial infarction (MI) is one of the major causes of death all over the world. Because MI frequently occurs suddenly without any preceding clinical symptoms, the prediction of MI is clinically of great importance. Angiotensin II is produced primarily by angiotensin I-converting enzyme (ACE) within atherosclerotic lesions and ACE level correlates with the severity of vessel wall damage. We analyzed the evolution with age of the frequencies of the I/D polymorphism of the ACE, A1166C of the angiotensin II AT1 receptor (AT1R), and M235T of the angiotensinogen (AGT) gene in a healthy population and he subsequent comparison to age- and sex-matched groups of MI patients. To investigate the influence of increasing age on the incidence and remaining lifetime risk of myocardial infarction in a cohort of older men. Polymorphisms of the AGT, ACE (I/D) and AGTR1 (A1166C) genes in patients and controls were analyzed using allele-specific PCR, and PCR-rflp. A total of 140 healthy subjects and 119 individuals with MI were divided into two groups < 65 and > 65 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the ACE I allele (P < 0.05) frequency decreased with age. The TT genotype frequency increased in patients with MI > 65 years (OR = 3.52; 95% CI; 3.12–5.54). The AA genotype showed a similar behaviour (OR = 2.9; 95% CI; 1.11–5.6). The DD genotype increased in the MI > 65 group (OR = 6.66; 95% CI; 2.02–21.9). Serum ACE activity was positively associated to age (r = 0.38, p = 0.000). Patients with DD genotype > 65 years was significantly higher (119.7 ± 50.8 U/L) than in patients with DD genotype < 65 years (96.9 ± 31.4 U/L, p = 0.039). The incidence of new cardiovascular disease continued to increase after age 65 but was most often diagnosed at death. These findings suggest that people aged 60 and older have a substantial amount of undiagnosed disease. We propose that the study of the allele frequency evolution in an healthy population at different ages is essential to determine risk factors for MI in case-control studies.

One-Week Antihypertensive Effect of Ile-Gln-Pro in Spontaneously Hypertensive Rats

The antihypertensive effect of an angiotensin I-converting enzyme (ACE) inhibitory peptide Ile-Gln-Pro (IQP), whose sequence was derived from Spirulina platensis , was investigated in spontaneously hypertensive rats (SHRs) for 1 week. The weighted systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the peptide IQP-treated group were significantly lower than those of the negative control group from the third and fourth days, respectively. Accompanying the blood pressure reduction, a significant regulation of the expression of major components of the renin-angiotensin system (RAS) was found in the treatment group, including downregulation of the mRNA levels of renin, ACE, and the angiotensin II type 1 (AT1) receptor in the kidney, as well as serum angiotensinogen (Ang), ACE, and angiotensin II (Ang II) concentrations. The treatment group also showed upregulation of mRNA expression of the angiotensin II type 2 (AT2) receptor in the kidney. Our findings suggested that IQP might be of potential use in the treatment of hypertension.

ACE gene polymorphism and serum ACE activity in Iranians type II diabetic patients with macroalbuminuria

There are controversial results related to the contribution of insertion (I)/deletion (D) polymorphism of the angiotensin I-converting enzyme (ACE) in the development of diabetic nephropathy. To assess the distribution of this polymorphism in diabetic patients with and without nephropathy we studied 140 unrelated type 2 diabetic patients from the Kermanshah Province of Iran with ethnic background of Kurds including 68 patients with macroalbuminuria and 72 normoalbuinuric diabetic patients as controls. Genotyping was done by polymerase chain reaction (PCR). The frequency of D allele in nephropathic and normoalbuminuric patients were 69.1 and 58.3%, respectively (P=0.061). In individuals with DD genotype the risk of macroalbuminuria increased 2.87-fold (P=0.057). Significant lower level of serum ACE activity was found in the normoalbuminuric (59.76IU/l) compared to macroalbuminuric (97.43IU/l) patients. The serum ACE activity was significantly higher in macroalbuminuric patients with ID (105.7IU/l) and ID+DD (100.7IU/l) genotypes compared to normoalbuminuric patients with the same genotypes (63.5 and 64.2IU/l, respectively). Treatment with captopril significantly (P=0.045) reduced the serum ACE activity in normoalbuminuric patients with DD genotype compared to macroalbuminuric patients with the same genotype (33.6 vs. 73.8IU/l). However, the greatest benefit effect of losartan therapy on ACE activity was observed only in macroalbuminuric patients with DD genotype compared to that in normoalbuminuric patients (61.0 vs. 109.0IU/l, P=0.06). Our study suggests the importance of ethnic origin in the development of diabetic nephropathy and demonstrates different responses to therapy according to genotype and stage of diabetes.

Serum angiotensin I-converting enzyme activity in various pulmonary diseases (author's transl)

Serum angiotensin I-converting enzyme activity in various pulmonary diseases (author's transl)

Haplotype of growth hormone and angiotensin I-converting enzyme genes, serum angiotensin I-converting enzyme and ventricular growth: pathway inference in pharmacogenetics

An insertion/deletion (I/D) polymorphism in the angiotensin I-converting enzyme (ACE) gene is associated with variations in circulating and tissue angiotensin I-converting enzyme activity, and differences in exercise-induced left ventricular hypertrophic response. A genetic marker (CSH1.01) in the syntenic GH-CSH gene cluster correlates with metabolic syndrome in adult life in males. Approximately 24% linkage disequilibrium between CSH1.01T and D alleles of ACE I/D has also been reported. The objective was to examine the hypothesis that effects ascribed to ACE genotype may reflect causality in the GH-CSH cluster. The ACE I/D polymorphism and GH-CSH BglII-B single nucleotide polymorphism (in strong linkage disequilibrium with CSH1.01) were determined in 847 British Army recruits. Serum angiotensin I-converting enzyme activity and left ventricular mass were measured before and after a 12-week physical training program. Genotype and haplotype analyses of both markers were performed in relation to these phenotypes. The ACE I/D polymorphism was in linkage disequilibrium with BglII-B (D'=0.3). Strong association was seen between ACE I/D genotypes and serum angiotensin I-converting enzyme activity (P<0.0001), but not left ventricular mass change. BglII-B genotypes also associated significantly with serum angiotensin I-converting enzyme level (P<0.0001). Haplotype analysis, however, showed that most of this association resulted from linkage disequilibrium between BglII-B and ACE I/D. BglII-B did not associate with left ventricular mass change. GH-CSH BglII-B genotype associates significantly with angiotensin I-converting enzyme levels, but only through linkage disequilibrium with ACE I/D. Every phenotype with which ACE I/D has been associated merits investigation of potential causal effects originating in the GH-CSH cluster (and vice versa), otherwise the chain of causality could be misinterpreted.