ABSTRACT
<p><b>OBJECTIVE</b>To explore the role of the interaction between glycogen synthase kinase-3β (GSK-3β) and endoplasmic reticulum stress (ERS) in the high glucose (HG)-induced injury in human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>HUVECs treated with 40 mmol/L glucose for 24 h were examined for expression levels of GSK-3β, GRP78, CHOP and cleaved caspase-3 protein using Western blotting. The cell viability was examined using CCK-8 assay and cell apoptosis was detected with Hoechst 33258 nuclear staining and photofluorography. The intracellular level of reactive oxygen species (ROS) was measured with dichlorfluoresein staining and photofluorography. Mitochondrial membrane potential (MMP) was tested by rhodamine 123 (Rh123) staining and photofluorography.</p><p><b>RESULTS</b>Treatment of HUVECs with 40 µmol/L glucose for 3-24 h activated GSK-3β in a time-dependent manner, leading to significantly down-regulated expression of phosphorylated (p)-GSK-3β (P<0.05). HG exposure of the cells for 1-24 h induced ERS, evidenced by time-dependently up-regulated expression of GRP78 and CHOP (P<0.05). LiCl, an inhibitor of GSK-3β, attenuated HG-induced ERS and significantly lowered the expression levels of GRP78 and CHOP (P<0.01). 4-PBA, an inhibitor of ERS, obviously ameliorated the activation of GSK-3β by HG as shown by the increase in p-GSK-3β expression level (P<0.01). HG exposure for 24 h induced obvious injuries in HUVECs, which exhibited decreased cell viability, increased cell apoptosis, increased expression of cleaved caspase-3 and ROS generation, and loss of MMP. Pretreatment of the cells with LiCl or 4-PBA for 60 min before HG exposure significantly lessened the cell injuries (P<0.01).</p><p><b>CONCLUSION</b>Interactions between GSK-3β and ERS occur in HUVECs exposed to HG and participate in HG-induced cell injuries.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To explore whether angiotensin-(1-7) [Ang-(1-7)] protects cardiac myocytes against high glucose (HG)-induced injury by inhibiting ClC-3 chloride channels.</p><p><b>METHOD</b>H9c2 cardiac cells were exposed to 35 mmol/L glucose for 24 h to establish a cell injury model. The cells were treated with Ang-(1-7) or the inhibitor of chloride channel (NPPB) in the presence of HG for 24 h to observe the changes in HG-induced cell injury. Cell counter kit 8 (CCK-8) assay was used to test the cell viability, and the morphological changes of the apoptotic cells were detected using Hoechst 33258 staining and fluorescent microscopy. The intracellular level of reactive oxygen species (ROS) was examined by DCFH-DA staining, SOD activity in the culture medium was measured using commercial kits, and the mitochondrial membrane potential (MMP) of the cells was tested with rodamine 123 staining. The expression level of cardiac ClC-3 chloride channels was detected with Western blotting.</p><p><b>RESULTS</b>Exposure of H9c2 cardiac cells to 35 mmol/L glucose for 24 h markedly enhanced the expressions of cardiac ClC-3 channel protein (P<0.01). Co-treatment of the cells with 1 µmol/L Ang-(1-7) and HG for 24 h significantly attenuated HG- induced upregulation of ClC-3 channel protein expression (P<0.01). Co-treatment of the cells exposed to HG with 1 µmol/L Ang-(1-7) or 100 µmol/L NPPB for 24 h obviously ameliorated HG-induced injuries as shown by increased cell viability, enhanced SOD activity, decreased number of apoptotic cells, and reduced intracellular ROS generation and loss of MMP (P<0.01).</p><p><b>CONCLUSION</b>ClC-3 channels are involved in HG-induced injury in cardiac cells. Ang-(1-7) protects cardiac cells against HG-induced injury by inhibiting ClC-3 channels.</p>
ABSTRACT
Objective Giant left ventricle indicates severe or irreversible pathologic injury of the cadiocytes in the left ventricle.This study was to investigate the effects of cardiac valve replacement on the volume of the left ventricle and systolic function of the heart.Methods We retrospectively analyzed the clinical data about 41 cases of cardiac valve replacement for giant left ventricle (left ventricle end diastolic dimension LVEDD ≥ 70 mm and left ventricle end systolic dimension LVESD ≥ 50 mm).We compared the LVEDD,LVESD and left ventricular ejection fraction (LVEF) of the patients before and at 1 week,3 months and 1 year after operation.Results Compared with the baseline,LVEDD and LVESD were decreased significantly at 1 week,3 months and 1 year after operation in a timedependent manner (P＜0.01),while LVEF reduced at 1 week (P＜0.01),restored to the preoperative level at 3 months (P=0.10),and increased at 1 year postoperatively (P＜0.05).Based on the New York Heart Association (NYHA) functional classification,there were 16 cases of class Ⅱ,22 cases of class Ⅲ,1 case of class Ⅲ-Ⅳ,and 2 cases of class Ⅳ preoperatively.Follow-up was completed in 36 cases (87.8％),with a mean time of 50.03± 19.28 (12-95) months,during which 34 (94.4％) of the patients survived,including 24 cases of NYHA class Ⅰ and 10 cases of class Ⅱ,and 2 (5.6％) died,1 from chronic cardiac failure complicated by multiple organ failure and the other from liver cancer with systemic metastasis.Five (12.2％) of the cases were lost to follow up.Conclusion Cardiac valve replacement decreases the left ventricular volume of the patient with giant left ventricle in a time-dependent manner.The systolic function of the heart is reduced in the early postoperative period,which,however,may gradually improve with time and become better than the preoperative status.