ABSTRACT
Objective:The aims of the study were to investigate the relationship among atherogenic index of plasma (AIP) and inflammatory adipocytokines with the severity of coronary artery calcification (CAC) score in coronary artery disease (CAD). And then we analyzed the diagnostic value of the new markers on CAC.Methods:A total of 241 patients with CAD diagnosed by coronary CT angiography (CTA) and coronary angiography in Baoding First Central Hospital from June 2019 to June 2020 were retrospectively enrolled. According to the presence of calcification in coronary CTA, they were divided into CAC group ( n=63) and non-CAC group ( n=178). The clinical data of the patients were collected, and the levels of serum inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). The correlation between CAC score and AIP and inflammatory cytokines was analyzed. The diagnostic value of AIP and inflammatory factors in the formation of CAC in patients with CAD. Results:The levels of AIP, serum osteoprotegerin (OPG) and oligomeric matrix protein (COMP) in CAC group were higher than those in non-CAC group, while the levels of serum fibroblast growth factor 21 (FGF21) were lower than those in non-CAC group, with statistically significant difference (all P<0.01). Correlation analysis showed that CAC score of CAD patients was positively correlated with AIP, OPG and COMP ( r=0.581, 0.451, 0.326, P<0.05), and negatively correlated with FGF21 ( r=-0.294, P<0.05). Receiver operating characteristic (ROC) curve analysis showed that AIP, OPG, COMP and FGF21 had diagnostic value for CAC in CAD patients (all P<0.05). AIP>0.387, OPG>5.150 ng/ml, FGF21>136.35 pg/ml, COMP>733.16 ng/ml were independent factors affecting the formation of CAC (all P<0.05). Conclusions:The increase of AIP and the change of inflammatory factors can be used as markers for the diagnosis of CAC formation in CAD patients.
ABSTRACT
Objective To investingate the effect of low-density lipoprotein (LDL) on epithelial -mesenchymal transition and extracellular matrix (ECM) accumulation in human peritoneal mesothelial cells (HPMCs).Methods (1)HPMCs were randomly divided into control group,LDL group (100 mg/L) and LDL (100 mg/L) + lactoferrin (100 mg/L,LDL receptor blocking agent) group.After co-cultured for 24 h,the expression of LDL receptor in HPMCs was examined by immunofluorescence staining,and the LDL uptake by HPMCs was observed with oil red O staining.(2)HPMCs were cultured with different concentrations of LDL (0,25,50,100 mg/L).After co-cultured for 24 h,the change of cell morphology was observed by inverted phase contrast microscope,and the expression of α-smooth muscle actin (α-SMA) was examined by immunofluorescence.(3) HPMCs were randomly divided into control group (5.6 mmol/L glucose),mannitol group (M,2.18％ mannitol),low glucose group (LG,30 mmol/L),high glucose group (HG,120 mmol/L) and HG + LDL group (120 mmol/L glucose + 100 mg/L LDL).Cocultured for 48 h,the mRNA expression of α-SMA,E-cadherin and type 1 plasminogen activator inhibitor (PAI-1) was detected by real-time quantitative PCR,the protein expression of α-SMA was detected by Western blotting,the content of type I collagen (Col I) and PAI-1 in supernatant was detected by ELISA.Results (1) After co-cultured with LDL for 24 h,the expressin of LDL receptor was found on the cell membrane of HPMCs.Oil red staining showed that LDL could be uptaken into the cells and abolished by LDL receptor blocker.(2) HPMCs tended to be loosely intercellular connected to each ofher,and prsesnted significant formation of fibroblast-like spindle morphology.The cytoplasm immunofluorescence intensity of α-SMA gradually increased with the increase of LDL concentration.Compared to the control group,the expressions of α-SMA mRNA and protein were significantly increased,and the expression of E-cadherin mRNA was decreased in HG + LDL group(all P ＜ 0.05).But the expressions of the parameters above-mentioned were not significant different between HG group and HG + LDL group or between HG group and control group.(3) Compared with HG group or control group,the concentrations of Col Ⅰ [(19.27±0.17) μg/L vs (14.09±0.30) μg/L or (14.81±0.91) μg/L,all P ＜ 0.05] and PAI-1 [(498.24±76.91) ng/L vs (342.19±30.43) ng/L or (220.39±33.82) ng/L,all P ＜ 0.05] in supernatant of HPMCs were significantly up-regulated in HG + LDL group,meanwhile the expression of PAI-1 mRNA was significantly higer than that in control group (P =0.022).Conclusions HPMCs uptake LDL into cells via LDL receptors.LDL can induce HPMCs transdifferentiation in the condition of high glucose,increase the secretion of Col Ⅰ,inhibit the degradation of ECM through up-regulating the expression of PAI-1,and lead to ECM accumulation.