ABSTRACT
Objective :To study safety and effectiveness of vitamin D combined benazepril on patients with essential hyper-tension (EH) and positive urine microalbumin (UMA).Methods :A total of 92 EH patients with positive UMA were ran-domly divided into benazepril group (n＝44 , received benazepril 5md/d ,placebo 1 capsule/d) and combined treatment group (n＝48 , received vitamin D3 400mg/d and benazepril 5mg/d) ,both groups were treated for 12 weeks.Levels of mean arterial pressure (MAP) ,serum creatinine (SCr) and UMA were measured and compared between two groups before and after treatment .Results :Compared with before treatment ,there were significant reductions in levels of MAP and UMA in two groups after treatment , P＝0.001 all ;compared with benazepril group ,there were significant reductions in levels of MAP [ (108.45 ± 15.09) mmHg vs.(101.1 ± 15.02) mmHg] and UMA [ (52.35 ± 17.45) mg/L vs.(43.75 ± 13.29) mg/L] in combined treatment group ,P＜0.05 or ＜0.01.There was no significant difference in SCr level between two groups before and after treatment , P＞0.05 all.Conclusion : Compared with pure benazepril antihypertensive treat-ment ,vitamin D combined benazepril possesses better therapeutic effect on reducing UMA and antihypertensive effect .And it is safe without obvious damage on kidney function ,which is worth extending .
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of liver X receptors (LXRs) on endothelin-1 (ET-1) induced murine HL-1 cardiomyocytes hypertrophy.</p><p><b>METHODS</b>Cultured murine HL-1 cardiomyocytes were divided into four experiment groups: (1) CONTROL GROUP:treated with DMSO; (2) T0901317 group:treated with LXRs agonist T0901317 (1 µmol/L); (3) ET-1 group:treated with ET-1 (1 nmol/L); (4) T0901317 + ET-1 group:treated with T0901317 (1 µmol/L) for 8 hours, then treated with ET-1 (1 nmol/L). Twenty-four hours later, immunofluorescent staining was performed on HL-1 cells, the surface area of HL-1 cells was analyzed with NIH Image J software, and the synthetic rate of protein in HL-1 cells was detected by (3)H-leucine incorporation. The mRNA level of atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MyHC) was measured by quantitative realtime PCR. The effect of T0901317 on mRNA expression of ANP was also detected after LXRs gene silencing.</p><p><b>RESULTS</b>The surface area of HL-1 cells, mRNA expression of ANP and β-MyHC, and (3)H-leucine incorporation in ET-1 group were 2.00 ± 0.29, 1.98 ± 0.47, 2.13 ± 0.39 and 1.79 ± 0.17, respectively, which were significantly higher than those of control group (1.00 ± 0.26, 1.00 ± 0.21, 1.00 ± 0.31 and 1.00 ± 0.03, respectively, all P < 0.05). Compared with ET-1 group, the surface area of HL-1 cells, mRNA expression of ANP and β-MyHC, and (3)H-leucine incorporation were significantly decreased in T0901317 + ET-1 group (1.24 ± 0.25, 1.19 ± 0.21, 1.48 ± 0.27 and 1.15 ± 0.11, respectively, all P < 0.05). After inhibition of LXRα/β expression in HL-1 cardiomyocytes using the specific siRNAs, the mRNA expression of ANP in T0901317 + ET-1 group was 1.78 ± 0.05, which was similar as that in ET-1 group (1.94 ± 0.17, P > 0.05).</p><p><b>CONCLUSION</b>T0901317, an agonist of LXRs, could inhibit ET-1 induced cardiac hypertrophy in vitro, and LXR ligand-mediated inhibition on ANP mRNA expression by T0901317 is receptor dependent.</p>
Subject(s)
Animals , Mice , Cardiomegaly , Metabolism , Cell Line , Endothelin-1 , Metabolism , Hydrocarbons, Fluorinated , Pharmacology , Liver X Receptors , Myocytes, Cardiac , Metabolism , Orphan Nuclear Receptors , Metabolism , Signal Transduction , Sulfonamides , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To observe the relationship between serum and monocyte-derived-macrophages secreted adipocyte fatty acid binding protein (A-FABP), adiponectin (or A-FABP/adiponectin ratio) and coronary artery disease.</p><p><b>METHODS</b>Three hundred and forty subjects underwent coronary angiography (CAG) were classified into CAD group (n = 211) and non-CAD group (n = 129) according to the CAG results. The severity of coronary artery stenosis was assessed by the numbers of involved coronary artery branches and the sum of the Gensini scores. Fasting venous blood was collected from all subjects and peripheral monocytes were isolated from 20 subjects (10 selected from each group with age-, gender-, and BMI-matched). Peripheral blood monocytes were obtained and stimulated into macrophages with PMA, cell culture supernatant was collected. The concentration of serum/supernatant A-FABP and adiponectin levels were assayed by enzyme-linked immunosorbent assays.</p><p><b>RESULTS</b>(1) A-FABP levels tended to be higher in CAD patients compared to non-CAD subjects [18.3(13.2, 22.8) µg/L vs. 16.4(13.5, 20.4) µg/L, P = 0.088]. The concentration of adiponectin in CAD group was significantly lower than those in non-CAD group [13.9 (9.8, 17.1) mg/L vs. 19.7 (14.5, 27.6) mg/L, P < 0.05]. (2) The A-FABP levels increased and the adiponectin levels decreased as the number of stenotic vessels increased. Gensini scores were positively correlated with serum A-FABP (r = 0.120, P = 0.043) and inversely correlated with adiponectin (r = -0.405, P = 0.007). (3) The difference in A-FABP/adiponectin ratio was more prominent between subjects with CAD and subjects without CAD [(1.51 ± 0.79) µg/mg vs. (0.89 ± 0.30) µg/mg, P < 0.01] and there was a stronger positive correlation of Gensini score to A-FABP/adiponectin ratio(r = 0.531, P = 0.000). (4) Monocyte-derived-macrophages from patients with CAD had higher A-FABP/adiponectin ratio than that in patients without CAD [(0.51 ± 0.19) µg/mg vs. (0.36 ± 0.11) µg/mg, P < 0.05].</p><p><b>CONCLUSIONS</b>Increased levels of serum A-FABP and reduced levels of adiponectin in CAD patients serves as a novel biomarker for the severity of the coronary stenosis. A-FABP/adiponectin ratio is superior to A-FABP or adiponectin alone on predicting CAD risks.</p>