RESUMEN
Atherosclerosis chiefly results from inflammation as well as vascular endothelial cell dysfunction. Methylation levels of neuronally expressed developmentally downregulated 4 (NEDD4) were found to be fortified in atherosclerosis patients and NEDD4 deficiency enhanced vascular calcification. However, the exact function of NEDD4 in inflammation and vascular endothelial dysfunction remains to be elucidated. In the present study, CCK-8 assay was used to estimate cell viability. Reverse transcription-quantitative PCR was adopted to examine the expression of NEDD4, inflammation-associated enzymes and apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1). Western blotting was used to test NEDD4, endothelial nitric oxide synthase, inducible nitric oxide synthase and APEX1 protein levels. Cytotoxicity was detected by a lactate dehydrogenase (LDH) kit. Reactive oxygen species level was tested by a corresponding kit. Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 contents were examined with ELISA. Cell adhesion assays evaluated the adhesion of endothelial cells. Co-immunoprecipitation assay was used to test the relationship between NEDD4 and APEX1. The data revealed that NEDD4 expression rapidly declined in oxidized low density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs). Following NEDD4 overexpression, the active damage, inflammatory release and endothelial cell dysfunction in ox-LDL-induced HUVECs were attenuated. After co-transfection of APEX1 interference plasmids and NEDD4 overexpression plasmids, cell damage, inflammatory release and endothelial cell dysfunction in ox-LDL-induced HUVECs were improved again. Taken together, NEDD4 attenuated ox-LDL-induced inflammation and endothelial dysfunction by regulating APEX1 expression.
RESUMEN
Patients with acute coronary syndrome (ACS) have an increased serum level of calprotectin. The purpose of present study was to analyze the prognostic significance of serum calprotectin levels in elderly diabetic patients underwent percutaneous coronary intervention (PCI) due to ACS.A total of 273 consecutive elderly diabetic patients underwent PCI for primary ACS were enrolled. Serum calprotectin levels were measured before PCI, and baseline clinical characteristics of all patients were collected. All patients were followed up at regular interval for major adverse cardiovascular events (MACEs) during 1 year after PCI. MACEs include cardiovascular death, nonfatal myocardial infarction, and target vessel revascularization (TVR). The predicting value of serum calprotectin for MACEs was analyzed by using univariate and multivariate analysis and receiver-operating characteristic curve (ROC).At the endpoint of this study, 47 patients of all 273 patients had MACEs. According to optimal cutoff value of calprotectin for predicting MACEs by ROC analysis, all patients were stratified into a high calprotectin group and a low calprotectin group. The incidence rate of MACEs and TVR in high calprotectin group was prominently higher than that in low calprotectin group (21.9% vs 11.5%, Pâ=â.02). In multivariable COX regression analysis adjusting for potential confounders, serum calprotectin level remains as an independent risk predictor of MACE (hazard ratio, 1.56; 95% confidence interval [CI]: 1.08-4.62; Pâ=â.01).In diabetic patients with a comorbidity of ACS, a high serum level of calprotectin is associated to a higher MACE rate after PCI.