| Objectives To investigate the changes in serum levels of angiotensin-converting enzyme(ACE), Angiotensin(Ang)Ⅱ, ACE2, and Ang(1-7) and theirs relationship to cardiac structural and functional parameters in patients with essential hypertension(EH). To explore whether the possible mechanisms by which they modulate hypertensive heart disease(HHD) involve interaction, blood pressure(BP), N-terminal pro-brain natriuretic peptide(NT-pro BNP), inflammation, and extracellular matrix(ECM) remodeling.Methods We consecutively enrolled hypertensive patients and age- and sex-matched healthy subjects served as controls in North China University of Science and Technology Affiliated Hospital from March 2015 to December 2015. Baseline clinical data were collected and serum biochemical indices were measured by routine methods. Serum concentration levels of ACE, AngⅡ, ACE2, and Ang(1-7) were determined using commercially available ELISA kits. Serum concentration levels of NT-pro BNP, highsensitivity C-reactive protein(hs-CRP), and procollagen Ⅲ N-terminal peptide(PⅢNP) in hypertensive patients were also assayed. Cardiac structural and functional parameters were measured by echocardiography.Results 1 A total of 161 patients [81 males(50.3%), 80 females(49.7%); mean age 59±8 years] and 47 control subjects [19 males(40.4%), 28 females(59.6%); mean age 57±7 years] were enrolled. 2 Serum levels of ACE2 were significantly higher in patients than in control group [170.31(83.50~707.12) vs. 59.28(39.71~81.81) pg/ml, respectively, P<0.001]. The ratio of ACE2/Ang(1-7) levels was significantly higher in patients than in control group [0.14(0.07~0.59) vs. 0.05(0.04~0.07), P<0.001]. The ratio of ACE/ACE2 levels was significantly lower in patients than in control group [894.07(217.58~1688.65) vs. 2381.90(1628.43~4053.02), P<0.001]. 3 In patients, after adjustment of confounders, ACE was positively associated with interventricular septal thickness(IVST), while was negatively associated with aortic root dimension(AOD); AngⅡ was positively associated with IVST and left ventricular(LV) posterior wall thickness(LVPWT); ACE2 was positively associated with left atrial diameter(LAD), LV end-diastolic diameter(LVEDD), LV end-systolic diameter(LVESD), and LV mass(LVM), while was negatively associated with LV ejection fraction(LVEF); higher Ang(1-7) levels were related to abnormal E/A ratio. 4 In male patients, both AngⅡ and Ang(1-7) levels were negatively correlated with systolic BP(SBP)(rs=-0.339, P=0.002; r=-0.231, P=0.038), while ACE levels were negatively correlated with diastolic BP(DBP)(r=-0.268, P=0.015). In patients, AngⅡ levels were positively correlated with ACE2 levels(rs=0.341, P<0.001); both ACE2 and Ang(1-7) levels were negatively correlated with log(NT-pro BNP)(rs=-0.284, P<0.001; r=-0.174, P=0.028); four RAS components levels were neither related to serum hs-CRP nor to PⅢNP levels.Conclusions 1 In patients with EH, elevated circulating ACE2 concentration level accounted for RAS imbalance characterized by a relative decrease in ACE/AngⅡ level and an increase in ACE2/Ang(1-7) level. 2 In patients with EH, serum ACE concentration was independently and positively associated with IVST, while was independently and negatively with AOD; AngⅡ concentration was independently and positively associated with IVST and LVPWT; ACE2 concentration was independently and positively associated with LAD, LVEDD, LVESD, and LVM, while was independently and negatively with LVEF; elevated Ang(1-7) concentration level was independently associated with increased risk of LV diastolic dysfunction(reflected by E/A ratio). 3 In patients with EH, serum levels of ACE, AngⅡ, and Ang(1-7) were negatively correlated with BP in men; AngⅡ levels were positively correlated with ACE2 levels; both ACE2 and Ang(1-7) levels were negatively correlated with serum NT-pro BNP levels. |
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