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BACKGROUND: Recent studies have found that GPE-AGTshRNA nanocomposite cannot only have better transfection efficiency and lower cytotoxicity to hepatocytes in vitro, and also significantly reduce the expression of angiotensinogen at the gene and protein levels. OBJECTIVE: To observe the effects of angiotensinogen-targeted RNA interference on blood pressure and cardiac protection in spontaneously hypertensive rats, attempting to find a new antihypertensive strategy. METHODS: Spontaneously hypertensive rats were randomly evenly divided into gene therapy group, negative control group and blank control group, and normal Wistar Kyoto rats (WKY) were set as normal blood pressure control group (WKY group). There were nine sessions in total, with 10 days as one session. On the 1st day of each session, administration in each group was given via the rat tail vein: 500 μL of sterile water for injection in the WKY group, 500 μL of GPEAGTshRNA nanocomplex in the gene therapy group, and 500 μL of GPE-NC shRNA nanocomplex in the negative control group, and 500 μL of sterile water in the blank control group. We used real-time PCR and western blot assay respectively to detect hepatic angiotensinogen mRNA and protein levels. The serum levels of angiotensinogen and angiotensin II were measured by ELISA. Systolic blood pressure of the tail artery was measured with tail cuff method. Ventricular function was detected by echocardiography. Myocardial lesion was observed under light microscopy. RESULTS AND CONCLUSION: Angiotensinogen mRNA and protein expression and serum angiotensinogen and angiotensin II levels were significantly lower in the gene therapy group than the negative and blank control groups (P < 0.01). On the 3rd day after the first injection, tail arterial pressure of rats decreased significantly by (28±4) mmHg in the gene therapy group, which was significantly different from that before treatment (P < 0.01). The parameters of left ventricular ejection fraction and left ventricular fractional shortening were significantly increased in the gene therapy group, while the thickness of the left ventricular posterior wall was significantly reduced, and cardiomyocyte hypertrophy were significantly relieved under light microscope. To conclude, angiotensinogen-targeted RNA interference can effectively control blood pressure through downregulation of angiotensinogen, and meanwhile significantly alleviate myocardial hypertrophy and improve ventricular function. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between peripheral blood angiotensin converting enzyme (ACE) gene 1/D, angiotensinogen (AGT) gene M235T polymorphism and hypertensive disorder complicating pregnancy (HDCP) Methods Totally 200 HDCP patients (observation group) and 200 healthy pregnant women (control group) were selected. Peripheral venous blood samples were collected. NaPshot genotyping technique was used to analyze ACE gene 1/D and AGT gene M235T polymorphism. Serum ACE and AGT were detected by ELISA. Genotype distribution, allele frequency and serum ACE and AGT levels of different genotypes were compared between the two groups. The clinical data of HDCP patients were collected, including pre-pregnancy body mass index (BMI), number of passive smoking cases, family history of hypertension, systolic blood pressure, diastolic blood pressure, parity, TC, TG, creatinine (Cr), etc. The above clinical data of the two groups were compared, and the statistically significant differences as well as the polymorphism of ACE gene 1/D and AGT gene M235T in peripheral blood were incorporated into the multivariate Logistic regression model to analyze the risk factors affecting the incidence of HDCP. Results The distribution of ACE gene 1/D and AGT gene M235T polymorphism in the peripheral blood of the two groups was in accordance with Hardy Weinberg's law of genetic balance, which was representative of the population. The differences of ACE gene 1/D, AGT gene M235T genotype distribution and allele frequency between the two groups were statistically significant (all P < 0. 05). The serum levels of ACE and AGT in HDCP patients with genotype 1/D DD of ACE gene were higher than those with genotype DI and II, and those with M235T TI genotype of AGT gene were higher than those with genotypes MM and MT (all P < 0. 05). Univariate analysis showed that the pre-pregnancy BMI, the number of cases of passive smoking, the number of cases with family history of hypertension, systolic blood pressure, diastolic blood pressure, parity and Cr in the observation group were higher than those in the control group (all P < 0. 05), while no significant difference was found in the pregnancy times, TC or TG between the two groups (all P > 0. 05). Multivariate Logistic regression analysis showed that pre-pregnancy BM!, passive smoking, parity, ACE gene 1/D polymorphism and AGT gene M235T polymorphism were the risk factors of HDCP (all P < 0. 01). In ACE gene 1/D polymorphism of the peripheral blood, the risk of HDCP in pregnant women carrying genotype DD was 1. 324 times that of genotype II, and in AGT gene M235T polymorphism of the peripheral blood, the risk of HDCP in pregnant women carrying TI genotype was 1. 905 times that of MM genotype. Conclusion The 1/D of ACE gene and M235T polymorphism of AGT gene in the peripheral blood are associated with HDCP, and the risk of HDCP is higher in pregnant women with genotypes DD and TI. [ABSTRACT FROM AUTHOR]

Objective To explore the relationship between angiotensinogen (AGT) M235T gene polymorphism and severe preeclampsia. Methods We selected 133 pregnant women with severe preeclampsia (observation group) who would undergo elective cesarean section and 93 normal pregnant women undergoing cesarean section (control group) , and collected peripheral venous blood (3 mL) on the morning of operation day without uterine contraction. The genotype and allele distribution of M235T locus of AGT gene were detected py polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP ). ResultsThere were significant differences in genotype and allele distribution of M235T locus of AGT gene between the two groups (X2=6.219, 5.461 , respectively; both P <0. 05). The risk of severe preeclampsia in patients with MT genotype was 2. 284 times higher than that of patients with MM genotype (corrected OR =2. 284, 95% CI; 1. 169 -4.461 , P <0.05), and the risk of TT genotype was 3.910 times higher than that of MM genotype (corrected OR = 3.910, 95% CI: 1.532 -9.982, P<0.01 ). Comparisons of theoretical and actual values of MM, MT and TT genotypes between the two groups were all more than 0. 05 , which was in accordance with Hardy-Weinberg equilibrium law. Conclusion The M235T polymorphism of AGT gene is associated with the onset of severe preeclampsia, especially TT genotype. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the predictive factors for acute kidney injury (AKI) in patients with liver cirrhosis. MethodsA total of 105 patients with decompensated liver cirrhosis who visited Beijing YouAn Hospital from May 2017 to April 2018 were enrolled. These patients were divided into AKI group (n=49) and non-AKI group (n=56). Their general information and laboratory results were collected, and urine samples were collected on admission to measure urinary angiotensinogen (AGT), urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary kidney injury molecule-1 (KIM-1), which were corrected for urinary creatinine (UCr). The t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data; the chi-square test was used for comparison of categorical data between groups. A multivariate logistic regression analysis was performed. The receiver operating characteristic (ROC) curve was plotted to evaluate predictive efficiency. ResultsCompared with the non-AKI group, the AKI group had significantly higher proportions of patients with upper gastrointestinal bleeding and spontaneous bacterial peritonitis (χ2=11.420 and 8.083, both P＜0.05), significantly higher levels of leukocyte count, total bilirubin, direct bilirubin, urea nitrogen, and serum creatinine (SCr) (Z=-3.401, -2.082, -2.207, -5.872, and -7.460, all P＜0.05), and a significantly lower level of blood sodium (t=-4.905, P＜0.05). The AKI group had significantly higher urinary NGAL/UCr and urinary KIM-1/UCr than the non-AKI group (Z=-7.654 and -2.395, both P＜0.05). The multivariate analysis showed that SCr, blood sodium, and urinary NGAL/UCr were independent predictive factors for AKI in patients with liver cirrhosis (all P＜0.05). The ROC curve analysis showed that at the cut-off value of 88.1 μmol/L, SCr had a sensitivity of 93%, a specificity of 82%, and an area under the ROC curve (AUC) of 0.915 (95% confidence interval ［CI］: 0.850-0.980) in predicting AKI; at the cut-off value of 1.62 μg/g, urinary NGAL had a sensitivity of 87%, a specificity of 81%, and an AUC of 0.950 (95% CI: 0.911-0.989) in predicting AKI; urinary NGAL combined with SCr had an AUC of 0.964 (95% CI: 0.931-0.998). ConclusionUrinary NGAL is an independent risk factor for AKI in patients with liver cirrhosis and can be used for the early diagnosis of AKI in these patients. Urinary AGT and KIM-1 cannot independently predict the development of AKI in liver cirrhosis, and their application value awaits further exploration. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of paeonol on renin-angiotensin system (RAS) occurred on the development of ventricular remodeling after acute myocardial infarction (AMI) in rats. Methods The left anterior descending coronary artery was ligated to establish the model of AMI in male SD rats. Six groups were set up: sham-operation group, AMI model group, captopril control group, paeonol low dose group (6 mg/kg), paeonol middle dose group (9 mg/kg) and paeonol high dose group (12 mg/kg). Rats were given treatment for 4 weeks after the AMI model was established. HE staining was used to observe changes of myocardial tissue. Real-time PCR was used to detect the mRNA levels of angiotensinogen (AGT), angiotensin Ⅱ receptor type1(AGTR1) and endothelin (ET)-1 of six groups. Western blot assay was used to detect the protein levels of peptidyl-dipeptidase A (ACE), angiotensin Ⅱ(Ang)-Ⅱ and AGTR1 in six groups. Results The transcription of AGT, AGTR1, ET-1mRNA and the expressions of ACE, Ang-Ⅱ and AGTR1protein were significantly higher in myocardial tissue of AMI rats than those of sham-operation rats (P < 0.05). Compared with model group, the expressions of AGT, AG⁃TR1, ET-1mRNA and ACE, Ang-Ⅱ, AGTR1 protein were significantly decreased in paeonol high dose group and captopril control group (P < 0.05). Paeonol reduced the expressions of those mRNA and protein levels in a significant dose dependent manner. Conclusion Paeonol can slow down the deterioration of the ventricular remodeling after AMI in rats, which may be related to the inhibition of over-activation of RAS. [ABSTRACT FROM AUTHOR]

Objective To investigate the correlation between angiotensinogen gene M235T polymorphism and gerontism hypertension combined with depression. Methods The polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) technique were used to detect the M235T genetic polymorphism in 117 patients with hypertension and 91 patients with hypertension and depression, and 101 healthy subjects without clinical evidence of hypertension and depression. Result The frequency of TT genetype and T allele was higher in group with hypertension and the group with hypertension and depression than that in the control group (P < 0.05). Conclusion Angiotensinogen gene M235T polymorphism is significantly correlated with the gerontism hypertension combined with depression. [ABSTRACT FROM AUTHOR]

Objective: To explore the association between preeclampsia/eclampsia and maternal and fetal angiotensinogen SNPs. Methods: From January 2008 to October 2015, a case-parents/mother-control designed study was conducted among 347 preeclampsia/eclampsia cases and 700 controls to collect related information on their demographic characteristics and to detect the related angiotensinogen SNPs' genotypes. Both log-linear and unconditional logistic regression methods were employed to investigate the genetic effects of maternal/fetal angiotensinogen SNPs on preeclampsia/eclampsia. Multivariate binary unconditional logistic regression model and covariance were used to analyze the relationship between BMI before pregnancy, weight gain during pregnancy and overweight and obesity in preschool children. Results: Both fetal angiotensinogen rs3789679 GA and AA genotype were associated with the reduced risks of preeclampsia/eclampsia, with OR s as 0.73 (95 %CI : 0.55-0.96) and 0.62 (95 %CI : 0.39-0.98), respectively. For fetal angiotensinogen rs2493132, individuals that carrying the TT genotype, presented a positive association with the risk of preeclampsia/eclampsia, with OR as 1.60 (95 %CI : 1.08-2.37). However, these associations were not statistically significant after the correction of the false discovery rate. It was observed that fetal rs3789679 could reduce the risk of preeclampsia/eclampsia ( OR =0.73, 95 %CI : 0.55-0.96) under the dominant model (GA+AA/GG) while fetal rs2493132 increased the risk of preeclampsia/eclampsia ( OR =1.66, 95 %CI : 1.13-2.44) under the recessive model (TT/CC+CT). Maternal rs5051 presented an association with preeclampsia/eclampsia ( OR =1.33, 95 %CI : 1.01-1.76) under the dominant model (TC+CC/TT). Conclusions: Results from the dominant model showed that both fetal rs3789679 GA and AA genotype reduced the risk of preeclampsia/eclampsia and maternal rs5051 TC while CC genotype increased the risk of preeclampsia/eclampsia. Fetal rs2493132 TT genotype seemed to be associated with the risk of preeclampsia/eclampsia under the recessive model.

Objective: To investigate the relationship between angiotensin type I receptor (AGT I R) gene polymorphism and diabetic nephropathy (DN) and its progression., Methods: PCR technique was used to determine the AGT I R gene polymorphism in 86 patients without DN, 67 with microalbuminuria, 66 with clinical albuminuria and 20 type 2 DM patients with renal insufficiency., Results: In comparing the DN group with the non-DN group, it was found that there was a significant difference of the frequency of AC genotype with DN (chi(2) = 4.30, P < 0.05), and C mutative type was more frequent in the DN group (chi(2) = 3.97, P < 0.05). No significant difference of AGTIR-A1166-C genotype was found in cases with different durations of DN., Conclusion: Delete polymorphism of A1166-C gene is associated with DN in type 2 diabetes mellitus. It is suggested that detection of significant AGTIR-A1166-C polymorphism is of help for preventing DN in type 2 diabetes mellitus.