PURPOSE: Although it is well known thatmortality and morbidity due to cardiovascular diseases are higher in salt-sensitive subjects than in salt-resistant subjects, their underlying mechanisms related to obesity remain unclear. Here, we focused on salt-sensitive gene variants unrelated to monogenic obesity that interacted with sodium intake in humans. METHODS: This review was written based on the modified 3(rd) step of Khans' systematic review. Instead of the literature, subject genes were based on candidate genes screened from our preliminary Genome-Wide Association Study (GWAS). Finally, literature related to five genes strongly associated with salt sensitivity were analyzed to elucidate the mechanism of obesity. RESULTS: Salt sensitivity is a measure of how blood pressure responds to salt intake, and people are either salt-sensitive or salt-resistant. Otherwise, dietary sodium restriction may not be beneficial for everyone since salt sensitivity may be associated with inherited susceptibility. According to our previous GWAS studies, 10 candidate genes and 11 single nucleotide polymorphisms (SNPs) associated with salt sensitivity were suggested, including angiotensin converting enzyme (ACE), α-adducin1 (ADD1), angiotensinogen (AGT), cytochrome P450 family 11-subfamily β-2 (CYP11β-2), epithelial sodium channel (ENaC), G-protein b3 subunit (GNB3), G protein-coupled receptor kinases type 4 (GRK4 A142V, GRK4 A486V), 11β-hydroxysteroid dehydrogenase type-2 (HSD 11β-2), neural precursor cell-expressed developmentally down regulated 4 like (NEDD4L), and solute carrier family 12(sodium/chloride transporters)-member 3 (SLC 12A3). We found that polymorphisms of salt-sensitive genes such as ACE, CYP11β-2, GRK4, SLC12A3, and GNB3 may be positively associated with human obesity. CONCLUSION: Despite gender, ethnic, and age differences in genetics studies, hypertensive obese children and adults who are carriers of specific salt-sensitive genes are recommended to reduce their sodium intake. We believe that our findings can contribute to the prevention of early-onset of chronic diseases in obese children by facilitating personalized diet-management of obesity from childhood to adulthood.
Adult ; Angiotensinogen ; Blood Pressure ; Cardiovascular Diseases ; Child ; Chronic Disease ; Cytochrome P-450 Enzyme System ; Epithelial Sodium Channels ; Genetics ; Genome-Wide Association Study ; GTP-Binding Proteins ; Humans ; Hypertension ; Obesity* ; Oxidoreductases ; Peptidyl-Dipeptidase A ; Phosphotransferases ; Polymorphism, Single Nucleotide ; Sodium ; Sodium, Dietary

To study the expression of angiotensin converting enzyme 2 (ACE2) and angiotensin (Ang) 1-7 specific receptor Mas protain in renal blood vessels of metabolic syndrome ( MS) rats and its anti-oxidative effect. A total of 80 male SD rats were divided into four groups: the normal control group (NC, the same volume of normal saline), the MS group (high fat diet), the MS + Astragali Radix group (MS + HQ, 6 g x kg(-1) x d(-1) in gavage) and the MS + Valsartan group (MS + XST, 30 mg x kg(-1) x d(-1) in gavage). After four weeks of intervention, their general indexes, biochemical indexes and blood pressure were measured; plasma and renal tissue Ang II, malondialdehyde (MDA) and superoxide demutase (SOD) levels were measured with radioimmunoassay. The protein expressions of Mas receptor, AT1R, ACE and ACE2 were detected by western blot analysis. According to the result, compared with the NC group, the MS group and the MS + HQ group showed significant increases in systolic and diastolic pressures, body weight, fasting glucose, fasting insulin, triglycerides, free fatty acid and Ang II level of MS rats (P < 0.05). The MS + XST group showed notable decreases in systolic and diastolic pressures than that of the MS group. The MS group showed significant increases in the SOD activity and NO level and decrease in the MDA level after being intervened with Astragali Radix. ACE and AT1R protein expressions in renal tissues of the MS group were higher than that in the NC group, but with lower ACE2 and -Mas receptor expressions (all P < 0.05). Compared with the MS group, the MS + HQ group showed significant increase in Mas receptor expression in renal tissues, whereas the MS + XST group showed notable decrease in AT1R (all P < 0.05). In conclusion, Astragali Radix can increase the Mas receptor expressions in renal tissues, decrease ACE expression and change local Ang II, MDA, NO and SOD in kidneys, so as to protect early damages in renal tissues.
Angiotensin I ; metabolism ; Animals ; Astragalus Plant ; chemistry ; Blood Glucose ; metabolism ; Blood Pressure ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; injuries ; metabolism ; Male ; Malondialdehyde ; metabolism ; Metabolic Syndrome ; drug therapy ; genetics ; metabolism ; physiopathology ; Peptide Fragments ; metabolism ; Peptidyl-Dipeptidase A ; genetics ; metabolism ; Proto-Oncogene Proteins ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Signal Transduction ; drug effects

OBJECTIVETo investigate the effect of tanshinone II(A) on the expression of different components in the renin-angiotensin system of left ventricles of renal hypertensive rats.

METHODThe renal hypertension model was established in rats by the two-kidney-one-clip (2K1C) method. In the experiment, all of the rats were randomly divided into four groups (n = 15 per group) before the operation: the sham-operated (Sham) group, the hypertensive model (Model) group, the low-dose tanshinone II(A) group and the high-dose tanshinone II(A) group. At 5 week after the renal artery narrowing, the third and fourth groups were administered with 35 mg kg(-1) x d(-1) and 70 mg x kg(-1) x d(-1) of tanshinone II(A), respectively. The blood pressure in rats was determined by the standard tail-cuff method in each week after the operation. After the drug treatment for 8 weeks, all the rats were put to death, and their left ventricles were separated to determine the ratio of left ventricle weight to body weight (LVW/BW), the myocardial collagen content, and the expressions of different components in myocardial RAS, including angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), angiotensin 1-type receptor (AT1R), Mas receptor mRNA expression and angiotensin II (Ang II) and angiotensin (1-7) [Ang (1-7)] content.

RESULTCompared with the sham group, the hypertensive model group exhibited a markable increase in the content of Ang II and Ang (1-7) and the mRNA expressions of ACE, ACE2, AT1R and Mas (P < 0.01). However, the treatment with tanshinone II(A) showed the does dependence, inhibited left ventricle hypertrophy, decreased myocardial Ang II content and the mRNA expression of ACE and AT, R in renal hypertensive rats (P < 0. 01) , further increased the myocardial Ang (1-7) content and the mRNA expression of ACE2 and Mas (P < 0.01) , but without any change in the blood pressure of hypertensive rats.

CONCLUSIONThe treatment with tanshinone II(A) could inhibit left ventricle hypertrophy of renal hypertensive rats. Its mechanism may be partially related to the expression of different components in the renin-angiotensin system for regulating myocardial tissues.

Angiotensin I ; genetics ; metabolism ; Angiotensin II ; genetics ; metabolism ; Animals ; Blood Pressure ; drug effects ; Diterpenes, Abietane ; administration & dosage ; Heart Ventricles ; drug effects ; metabolism ; Humans ; Hypertension ; drug therapy ; genetics ; metabolism ; physiopathology ; Male ; Peptide Fragments ; genetics ; metabolism ; Peptidyl-Dipeptidase A ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Renin ; genetics ; metabolism ; Renin-Angiotensin System ; drug effects

Angiotensin-I converting enzyme (ACE) is a key regulator of blood pressure, electrolytes and fluid homeostasis through conversion of angiotensin I into angiotensin II. Recently, a genetic polymorphism of the ACE gene, which accounts for 47% of the variation of ACE activity in blood, has been advocated as a biomarker of athletic aptitude. Different methods of analysis and determination of ACE activity in plasma have been used in human and equine research without a consensus of a "gold standard" method. Different methods have often been used interchangeably or cited as being comparable in the existing literature; however, the actual agreement between assays has not been investigated. Therefore, in this study, we evaluated the level of agreement between three different assays using equine plasma obtained from 29 horses. Two spectrophotometric assays using Furylacryloyl-phenylalanyl-glycyl-glycine as substrate and one fluorimetric assay utilizing o-aminobenzoic acid-FRK-(Dnp)P-OH were employed. The results revealed that the measurements from the different assays were not in agreement, indicating that the methods should not be used interchangeably for measurement of equine ACE activity. Rather, a single method of analysis should be adopted to achieve comparable results and critical appraisal of the literature is needed when attempting to compare results obtained from different assays.
Animals ; Enzyme Assays/*methods ; Female ; Fluorometry/*methods ; Horses/blood/genetics/*metabolism ; Male ; Oligopeptides/pharmacology ; Peptidyl-Dipeptidase A/blood/genetics/*metabolism ; Polymorphism, Genetic ; Reference Values ; Spectrophotometry/*methods

OBJECTIVETo investigate the effect of astragaloside IV (As IV) on the activation of rennin-angiotensin system in rats with pressure-overload induced cardiac hypertrophy.

METHODLeft ventricle hypertrophy was induced by abdominal aorta banding between bilateral renal aortas for 12 weeks. Rats were given astragaloside IV 1.0 mg x kg(-1) and 3.3 mg x kg(-1) for 12 weeks, respectively. After treatment, the left ventricular mass index (LVMI)was calculated by morphometry methods. Plasma and cardiac tissue angiotensin II, and plasma aldosterone were measured by ELISA method. Gene expressions of ACE, AT1 and AT2 in cardiac tissue were detected by real time PCR. Protein expressions of AT1 and AT2 in cardiac tissue were detected by Western blot.

RESULTCompared with model rats, LVMI was decreased by astragaloside IV treatment. Biochemical results indicated that the contents of angiotensin II in plasma and cardiac tissue as well as aldosterone in plasma were all increased in abdominal aorta banding rats comparing with sham-operated rats, then, decreased by astragaloside IV treatment. Gene expressions of cardiac ACE was downregulated by astragaloside IV, however, gene and protein expressions of cardiac AT2 were upregulated by astragaloside IV. Both elevated gene and protein expressions of AT1 were not attenuated by astragaloside IV.

CONCLUSIONExcessive activated rennin-angiotensin system in rats with pressure-overload induced cardiac hypertrophy is inhibited by astragaloside IV treatment.

Aldosterone ; blood ; Angiotensin II ; blood ; metabolism ; Animals ; Blood Pressure ; physiology ; Cardiomegaly ; drug therapy ; Enzyme-Linked Immunosorbent Assay ; Hypertrophy, Left Ventricular ; drug therapy ; metabolism ; Male ; Peptidyl-Dipeptidase A ; genetics ; Polymerase Chain Reaction ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; genetics ; Receptor, Angiotensin, Type 2 ; genetics ; Renin-Angiotensin System ; drug effects ; Saponins ; therapeutic use ; Triterpenes ; therapeutic use

OBJECTIVETo investigate the relationship of disease severity with angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and serum ACE activity in preterm infants during the first 7 days of life.

METHODSACE genotypes were determined in 85 preterm infants admitted to the neonatal intensive care unit (NICU). Serum ACE activity was measured and disease severity was evaluated by the Neonatal Critical Score (draft) 1, 3 and 7 days after birth.

RESULTSOf the 85 preterm infants, DD genotype was found in 19 cases, ID genotype in 34 cases and II genotype in 32 cases. On the 1st day of life, serum ACE activity in the DD genotype (33.42+/-7.93 U/L) and the ID genotype groups (31.53+/-7.56 U/L) were significantly higher than that in the II genotype group (25.53+/-7.56 U/L) (P<0.01). After 3 and 7 days of life, serum ACE activity decreased in the three groups, but the DD genotype group remained the highest ACE activity, followed by the ID genotype and the II genotype groups. On the 1st day of life, the critical score of the DD genotype group (87.37+/-8.30) was lower than the ID genotype (95.82+/-5.85) and the II genotype groups (95.88+/-6.85) (P<0.01). On the 3rd day, the critical score of the DD genotype group was still lower than the ID genotype group (92.95+/-7.10 vs 96.94+/-5.85) (P<0.05).

CONCLUSIONSACE gene I/D polymorphism may be associated with the disease severity in preterm infants. The DD genotype carriers present more severe disease status, with higher serum ACE activity. Although the disease status can influence serum ACE activity, serum ACE activity is determined by the ACE genotype.

Female ; Humans ; Infant, Newborn ; Infant, Premature ; Intensive Care Units, Neonatal ; Male ; Peptidyl-Dipeptidase A ; blood ; genetics ; Polymorphism, Genetic ; Time Factors

Adult ; Genotype ; Humans ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; blood ; genetics ; Pneumoconiosis ; blood ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the association between angiotensin I-converting enzyme (ACE) gene and the levels of ACE and PAI-1 in Chinese Han patients with essential hypertension (EH) in Guangdong Province.

METHODSPolymerase chain reaction was used to examine the ACE genotype, colorimetry used to measure the serum ACE level, and spectrophotometric assay performed to examine the plasma PAI-1 level in 115 EH patients and 96 healthy controls in Guangdong Province.

RESULTSThe ACE DD genotype and D allele frequencies were significantly higher in EH group than in the control group (P<0.05), and the EH patients also had significantly higher serum ACE level and plasma PAI-1 level than the control subjects (P<0.01). The serum ACE level was positively correlated with plasma PAI-1 level in both EH group and control group (r=0.7913 and 0.7806, respectively, P<0.01). In EH group, the patients with DD genotype showed significantly higher serum ACE and plasma PAI-1 levels than those with ID and II genotypes (P<0.01), and patients with ID genotype had significantly higher ACE and PAI-1 levels than those with II genotype (P<0.05).

CONCLUSIONThe DD genotype and D allele of ACE gene can be risk factors for essential hypertension in Chinese Han subjects in Guangdong Province, and the EH patients have elevated serum ACE and plasma PAI-1 levels. Increased ACE level due to DD polymorphism may play an important role in elevating plasma PAI-1 level. The genetic variation of ACE contributes to the balance of fibrinolytic pathway, which may be one of the pathological mechanisms linking the ACE I/D genotype and EH.

Aged ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; blood ; genetics ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; blood ; genetics ; Plasminogen Activator Inhibitor 1 ; blood ; Polymorphism, Genetic ; Risk Factors

OBJECTIVE: To investigate the effect of angiotensin converting enzyme (ACE) in the pathogenesis of preeclampsia. METHODS: A cross-sectional study was conducted with 42 pregnant women in the following categories: 30 cases of preeclampsia (mild preeclampsia, n=15; severe preeclampsia, n=15), and normal pregnancy (control group,n=12). The expression and localization of ACE mRNA in the placenta of the 3 groups were respectively examined by in situ hybridization. Ultraviolet radiation colorimetry was used to detect the activity of ACE in the placenta tissue homogenate and the mothers' serum in the 3 groups. RESULTS: The expression of ACE mRNA was found in the endothelial cells of villus and trophoblasts in the placenta. The positive index of ACE mRNA in the placenta of preeclampsia(3.12+/-0.94) was higher than that in the normal pregnancies(1.65+/-0.67) (P<0.05), and there was significant difference between severe preeclampsia and mild preeclampsia (P<0.05). The levels of ACE activity in the placenta tissue homogenate and the maternal serum of preeclampsia were higher than those in the normal pregnancies (P<0.05), and there was significant difference between severe preeclampsia and mild preeclampsia (P<0.05). The placenta tissue homogenate ACE activity was correlated with ACE activity of the maternal serum (r=0.781,P<0.05). CONCLUSION The expression and activity of local ACE in the placenta tissue may play an important role in preeclampsia and contribute to the development of preeclampsia.
Adult ; Cross-Sectional Studies ; Female ; Humans ; In Situ Hybridization ; Peptidyl-Dipeptidase A ; blood ; genetics ; metabolism ; Placenta ; enzymology ; Pre-Eclampsia ; enzymology ; Pregnancy ; RNA, Messenger ; biosynthesis ; genetics

OBJECTIVETo investigate the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with type 2 diabetes mellitus (T2DM).

METHODSTwo hundred and nine patients with T2DM diagnosed based on the criteria for diabetes mellitus in 1999 by WHO and 221 controls were recruited from general population of Dongcheng District in Beijing. All subjects were genotyped for the I/D polymorphism of ACE gene by PCR-fragment length polymorphism (FLP) assay. Blood pressure, levels of plasma glucose, lipids and serum insulin were determined. Body mass index (BMI), waist-hip ratio (WHR) and homeostasis model assessment-insulin resistance index (HOMA-IR) were calculated.

RESULTSThe genotype frequencies for ACE genes DD, ID, and II were 19.1%, 42.1%, and 38.8% in patients, respectively, and 9.6%, 49.4%, and 41.0% in controls, respectively. The ACE DD genotype frequency was significantly higher in patients than in controls (chi2 = 7.61, P = 0.022). Multivariate logistic regression analysis showed that the ACE DD genotype was a risk factor for T2DM, with the OR of 2.35 (95% CI 1.17-4.71) adjusted for age, sex, BMI, WHR, blood pressure, and serum cholesterol levels.

CONCLUSIONThe ACE DD genotype is associated with the increased susceptibility to type 2 diabetes mellitus.

Adult ; Blood Glucose ; analysis ; Blood Pressure ; Body Mass Index ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Genetic Predisposition to Disease ; Genetic Testing ; Genotype ; Humans ; Insulin ; blood ; Insulin Resistance ; Lipids ; blood ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Risk Factors