Objective To study the association between the insertion(I)/deletion(D) polymorphism of the angiotensin-converting enzyme gene intron 16 (ACE/ID) and diabetic nephropathy (DN) among Chinese population by Meta-analysis. Methods Odds ratios of ACE/ID genotype distributions were analyzed in NIDDM or IDDM patients with and without DN. All the related studies on ACE/ID polymorphism and DN were identified while poor-qualified studies were excluded, and the risk of publication bias was estiMetad. The Meta-analysis software, RevMan 3.1, was applied for investigating heterogeneity among individual studies and summarizing effects across studies by proper statistical methods. Result The pooled odds ratios (with 95%CI) of DD vs ID + II and II vs ID + DD were 2.17 (1.74-2.70) and 0.49 (0.36-0.66) in NIDDM (12 studies), 3.92 (2.05-7.47) and 0.19 (0.09-0.43) in IDDM (3 studies) respectively (Plt;0.01). Conclusion In both NIDDM and IDDM, ACE/ID polymorphism is believed to be associated with diabetic nephropathy. The number of DN patients with DD genotype has been increased while that with II genotype decreased.
Objective To observe the expression of angiotensin-converting enzyme( ACE) and ACE2 in rat lung and kidney at different time point after smoke inhalation injury and to explore the possible mechanism. Methods Thirty healthy male SD rats were randomly divided into five groups( n = 6 in each group) , ie. a normal control group, and 4 injury groups of 1 h, 4 h, 10 h and 24 h respectively after 30 min of dense smoke inhalation. The rats were sacrificed at different time point. Lung and kidney tissue samples were collected for measurement of lung wet/dry weight ratio( W/D) , pathological study by HE staining, and ACE and ACE2 expression by immunochemistry staining. Results The inhaled rats all displayed acute lung injury symptoms. The lung W/D in the injury groups were significantly higher compared to the normal control group ( P lt; 0. 05, P lt; 0. 01) . ACE and ACE2 were expressed on cellular membrane of normal lung and kidney. The expression of ACE in lung was increased immediately after injury and the expression of ACE2 in lung was increased at 4 h after injury. No significant changes of the expression of ACE and ACE2 in kidney were observed in the five groups. Conclusion The imbalances of expression of ACE and ACE2 in lung might play an important role in the pathogenesis of smoke inhalation injury.
Objective To explore the role of renin-angiotensin system( RAS) in acute lung injury( ALI) /acute respiratory dysfunction syndrome( ARDS) by using amouse cecal ligation and puncture ( CLP)model.Methods The ALI/ARDS animal models were assessed bymeasuring blood gas, wet/dry lung weight ratio( W/D) , and lung tissue histology 18 hours after CLP operation. After the ALI/ARDS models was successfully established, immunohistochemistry, western blotting and radioimmunity were used to investigate the changes of several key enzymes of RAS, such as ACE, ACE2 and Ang Ⅱ. In addition, two groups of animals received a separate intraperitoneal injection of angiotensin-converting enzyme ( ACE) inhibitor captopril or recombinant mouse ACE2 ( rmACE2) after CLP, then the changes of RAS in ALI/ARDS modelswere observed. Results The extensive lung injuries can be observed in the lung tissues from CLP-treated animals 18 hours after operation. The CLP-induced ALI/ARDS led to an increase in the wet/dry weight ratio of the lung tissues, and a decrease in the PaO2 /FiO2 [ ( 194. 3 ±23. 9) mm Hg vs ( 346. 7 ±20. 5) mm Hg,P lt;0. 01] . Immunohistochemistry and western blotting tests of the lung tissues from CLP-treated animals showed a decrease in the ACE2 protein level. However, in both the CLP and sham mice there were no significant differences between the two groups. CLP markedly increased Ang Ⅱ level in lungs and plasma of mice, and RAS drugs significantly impacted the Ang Ⅱ levels of mice. Compared with the CLP group,captopril or rmACE2 led to a decrease of the Ang Ⅱ level in mice [ Lung: ( 1. 58 ±0. 16) fmol /mg,( 1. 65 ±0. 21) fmol /mg vs ( 2. 38 ±0. 41) fmol /mg; Plasma: ( 178. 04 ±17. 87) fmol /mL, ( 153. 74 ±10. 24) fmol /mL vs ( 213. 38 ± 25. 44) fmol /mL] . Conclusions RAS activation is one of the characteristics of CLP-induced ALI/ARDS in mice models. ACE and ACE2 in RAS have a different role in the regulation of AngⅡ synthesis, while ACE has a positive effect in generating AngⅡ, and ACE2 shows a negative effect.
Objective To explore the therapeutic effect of angiotensin-converting enzyme 2( ACE2) on pulmonary edema after sea-water drowning.Methods Twenty-four Wistar rats were randomly divided into 3 groups, ie. a control group, a seawater drowning group, and an ACE2 treatment group. The rats in the seawater drowning group and the ACE2 treatment group were infused sea-water into their lungs. Then the rats in the ACE2 treatment group were intraperitoneally injected with recombinant rat ACE2. All rats were killed at the time point of 3 hours. Rat arterial blood gas was analyzed and wet /dry weight ratio of lung tissue was measured. The IL-8 content in lung tissue was measured with enzyme linked immunosorbent assay. Pathological changes of lung tissue were observed under light microscope. Results Acute lung injury induced by seawater drowning was successfully reproduced in the rats. The PaO2 in the seawater drowning group was significantly lower than that in the control group and the ACE2 treatment group [ ( 52. 34 ±2. 69) mmHg vs. ( 96. 40 ±3. 47) mm Hg and ( 64. 58 ±3. 42) mm Hg, P lt;0. 05] . The lung W/D ratio and IL-8 level in the seawater drowning group were significantly higher than those in the control group and the ACE2 treatment group ( 8. 30 ±0. 24 vs. 4. 49 ±0. 19 and 5. 65 ±0. 25, P lt; 0. 05; 1112. 2 ±40. 02 vs. 440. 39 ± 4. 06 and 858. 56 ±9. 92, P lt;0. 05) . Lung pathological examination revealed hemorrhage and hyaline membrane formation, alveolar and interstitial edema in the seawater drowning group while those changes significantly relieved in the ACE2 treatment group. Conclusion ACE2 treatment has therapeutic effects on acute lung injury induced by seawater drowning.
Objective To compare the effectiveness and safety of angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) for coronary heart disease (CHD). Methods Randomized controlled trials (RCTs) on ARB vs. ACEI in treating CHD were collected in databases including MEDLINE, EMbase, BIOSIS Previews, The Cochrane Library, CBM, VIP, WanFang Data and CNKI from inception to July 2011, and the references of the included articles were also retrieved. In accordance with the Cochrane Handbook 5.0.1, two reviewers independently evaluated the quality of articles, and extracted and cross-checked the data. Then meta-analysis was performed using RevMan 5.1.1 software. Results A total of 18 RCTs (17 660 cases) were included. The results of meta-analysis showed that there were no significant differences between the ARB group and the ACEI group in all-cause mortality (RR=1.04, 95%CI 0.98 to 1.11, P=0.20), cardiovascular mortality (RR=1.04, 95%CI 0.97 to 1.12, P=0.26), myocardial infarction (RR=0.98, 95%CI 0.92 to 1.05, P=0.59), hospitalization for heart failure (RR=1.14, 95%CI 0.97 to 1.32, P=0.11) and stroke (RR=0.93, 95%CI 0.80 to 1.08, P=0.34). However, the risk of adverse events causing drug discontinuation was significantly lower in the ARB group compared with the ACEI group (RR=0.77, 95%CI 0.67 to 0.89, P=0.000 3). Conclusion Current evidence suggests that ARB is as effective as ACEI in reducing the risk of all-cause mortality, cardiovascular mortality, myocardial infarction, hospitalization for heart failure and stroke in patients with coronary heart disease. Moreover, it is much better in tolerance. Because of the quality limitation and sampling size of the induced studies, this conclusion still needs to be further proved by more large-scale, multicenter and perspective clinical trials.
Objective To systematically evaluate the effectiveness and safety of calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors (ACEIs) used alone v.s. used in combination on the reversion of left ventricular hypertrophy (LVH) in Chinese essential hypertension (EH) patients. Methods The following databases were searched, including, Cochrane Library (Issue 7, 2011), PubMed (1980 to 2011), EMbase (1990 to 2011), CBM (1978 to 2011), CNKI (1994 to 2011), VIP (1989 to 2011), and WanFang Data (1998 to 2011). The studies were screened, and the quality was evaluated according to predefined inclusion and exclusion criteria, and then Meta-analysis was conducted by using RevMan 5.1 software. Results A total of 10 studies involving 859 patients were included. The results of Meta-analysis showed that the CCBs plus ACEIs group (the combination group) was superior to the CCBs group in improving EH patients’ systolic pressure (SBP) (MD= –6.49, 95%CI –10.55 to –2.43), diastolic pressure (DBP) (MD= –4.48, 95%CI –6.76 to –2.21), left ventricular mass index (LVMI) (MD= –5.31, 95%CI –8.43 to –2.19), interventricular septal thickness (IVST) (MD= –1.33, 95%CI –2.00 to –0.66) and left ventricular posterior wall thickness (LVPWT) (MD= –0.87, 95%CI –1.41 to –0.33). In addition, compared with the ACEIs group, the combination group was greatly superior in decreasing LVMI (MD= –11.54, 95%CI –15.06 to –8.01), IVST (MD= –0.76, 95%CI –1.25 to –0.27) and LVPWT (MD= –0.80, 95%CI –1.01 to –0.59). But clinical effectiveness was similar between the combination group and the CCBs group or the ACEIs group in aspects of the left ventricular end diastolic diameter (LVEDD), fraction shortening (FS) and ejection fractions (EF) (Pgt;0.05). Conclusion The combination therapy of CCBs with ACEIs is superior to either the CCBs or the ACEIsmonothrepy in regression of left ventricular hypertrophy. Because of the low methodological quality and small sample, this conclusion needs to be proved by more high-quality, large-scale and multicenter randomized controlled trials in the future.
Objective To estimate the efficacy and tolerability of combination of Amlodipine and different angiotensin-converting enzyme inhibitors (ACEIs) in comparison with Amlodipine monotherapy in the treatment of hypertension. Methods We searched the Cochrane Central Register of Controlled Trials (Issue 2, 2009), PubMed, MEDLINE, EMbase, CBM, and CNKI (from their inception to August 2009) for relevant studies. Two reviewers independently retrieved randomized controlled trials (RCTs) according to the inclusion and exclusion criteria, assessed the methodological quality of included trials, and extracted data. Meta-analysis was performed by Stata 10.0 soft. Results Seventeen RCTs involving 3 291 patients were ultimately identified. The results of meta-analyses showed combination had a greater systolic blood pressure reduction (WMD=5.72, 95%CI 4.10 to 7.33, P=0.016) and diastolic blood pressure reduction (WMD=3.62, 95%CI 4.85 to 2.39, P=0.000) than monotherapy. Combination had fewer overall adverse events (RR=0.86, 95% CI 0.75 to 0.99) than that of monotherapy. Conclusion The results of meta-analyses indicate that combination provides a superior blood pressure control to that of monotherapy and has fewer adverse events and better tolerability in hypertensive patients.
Objective To evaluate the efficacy and safety of angiotensin-converting enzyme inhibitor (ACEI) on the left ventricular texture parameters, blood kinetics parameters, degree of cardiac function and rate of side effects of patients with heart failure when compared to angiotensin receptor blocker (ARB). Methods We searched MEDLINE (1966 to 2004), EMBASE (1989 to 2000), The Cochrane Library (Issue 1, 2004), IPA (1970 to 2004), and Chinese Biomedicine Database (1980 to 2003). The quality of included studies such as randomization, blinding, allocation concealment and loss of follow up was evaluated and meta-analysis was performd by RevMan 4.2 software. Results Eighteen randomized controlled trials (RCTs) were included. The meta-analysis of efficacy didn’t show statistical significance when comparing the pooled effect size of left ventricular end-diastolic diameter (LVEDD), cardiac output (CO), heart rate (HR), degree of cardiac function. The pooled RR rate of side effects was 2.17, 95%CI 1.53 to 3.07, P＜0.000 01. Conclusions No evidence shows significant difference of ACEI group from ARB group in the improvement of cardiac function and left ventricle remodeling. The rate of side effects of ACEI is statistically higher than that of ARB.
ObjectiveTo explore the therapeutic effect of angiotensin-converting enzyme 2 (ACE2) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a rat model. MethodsTwenty-four Wistar rats were randomly divided into a control group, an ALI group, and an ACE2 group.The rat ALI model was established by intravenous injection of LPS.Then the rats in the ACE2 group received intraperitoneally injection of recombinant rat ACE2 by 0.1 mg/kg immediately after LPS injection.All rats were sacrificed 2 hours later.Rat arterial blood gas was analyzed and wet/dry (W/D) weight ratio of lung tissue was measured.Concentrations of TNF-α, IL-8 and IL-1βin lung tissue homogenates were measured by ELISA.Pulmonary pathological changes were evaluated by hematoxylin-eosin stain under light microscope. ResultsALI induced by LPS was successfully established in the rats.ACE2 pretreatment markedly impoved PaO2 level of the ALI rats(P < 0.05), and decreased the lung W/D ratio(P < 0.05).The concentration of TNF-α, IL-8 and IL-1βin lung tissue homogenates were also inhibited by ACE2.And the lung histopathological changes and score were attenuated in the ACE2 group. ConclusionACE2 treatment has therapeutic effects on ALI induced by LPS.
ObjectiveTo assesse the association of an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) with the risk and the mortality of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). MethodsWe searched electronic databases through April 2014 for the terms "angiotensin-converting enzyme gene", "acute lung injury" and "acute respiratory distress syndrome", and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in adults. Eight studies met the inclusion criteria, comprising 498 ALI/ARDS patients, 3220 healthy controls and 1137 patients without ALI/ARDS. Three genetic models were used: the allele, dominant and recessive models. The meta-analysis was performed with RevMan 5.2 software. ResultsThe ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS compared with the healthy controls and the patient controls for any genetic model. The ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects, and OR was 2.99 (95% CI 1.87-4.76, P < 0.05), 0.36 (95% CI 0.20-0.67, P < 0.05), 4.62 (95% CI 1.71-12.45, P < 0.05) for allele I/D, genotype II/II+ID and genotype DD/II+ID, respectively. ConclusionThere is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians.