Background Remnant-like lipoproteins （RLPs） have been demonstrated to accelerate the onset of endothelial progenitor cells （EPCs） senescence. Recent study has determined that microRNAs （miRNAs） were closely asso...Background Remnant-like lipoproteins （RLPs） have been demonstrated to accelerate the onset of endothelial progenitor cells （EPCs） senescence. Recent study has determined that microRNAs （miRNAs） were closely associated with cellular proliferation and senescence. This study aimed to examine whether RLPs lead to an alteration of miRNAs in senescent EPCs. Methods RLPs were prepared from plasma samples with immunoaffinity method. After 8 days of culture, EPCs were identified by flow cytometry analysis. Cells were incubated with RLPs for 72 hours. The senescent markers p161NK4a and senescence-associated beta-galactosidase （SA-^-gal） were detected by Western blotting analysis and 13-gal staining assay, respectively. A human miRNA microarray containing 723 miRNAs was used to detect the expression profile of miRNAs in control and senescent EPCs. The result from the above microarray was qualified by RT-PCR assay. Results RLPs dose-dependently up-regulated the protein level of p16INK4a in EPCs, and RLPs at a concentration of 100 pg/ml induced a significant increase in the percentage of SA-i3-gal-positive EPCs. Of 723 miRNAs, four miRNAs expressed differentially and significantly in RLPs-treated EPCs （P 〈0.05）, then their changes in expression were validated by real-time RT-PCR. Among them miR-148b and miR-155 were upregulated while miR-574-3p was down-regulated significantly when compared with control （P 〈0.01）. Conclusions RLPs result in the onset of EPCs senescence. Senescent EPCs induced by RLPs exhibit a different profile of miRNAs. These three miR-148b and miR-155 and miR-574-3p reach a significant difference when compared with control, indicating that microRNA might take part in RLPs-induced EPCs senescence.展开更多
Objective::The purpose of this study was to determine the relationship between remnant-like particle cholesterol(RLP-C)and major adverse cardiovascular events(MACEs)in patients with different levels of proprotein conv...Objective::The purpose of this study was to determine the relationship between remnant-like particle cholesterol(RLP-C)and major adverse cardiovascular events(MACEs)in patients with different levels of proprotein convertase subtilisin/kexin 9(PCSK9).Methods::From September 2007 to January 2009,1,859 subjects in Pingguoyuan communities in Beijing were initially screened.After excluding those with bedridden status,mental illness,severe systemic diseases,and missing data,1,680 subjects were recruited for follow up.All recruited subjects were followed up from February 2013 to September 2013(181 subjects were lost to follow-up)and from June 2017 to September 2018(174 subjects were lost to follow up).Finally,1,325 subjects were included in the study.General demographic characteristics,lifestyle and behaviors,disease history and use of medication was collected.Levels of total cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,fast blood glucose,RLP-C,low-density lipoprotein triglycerides and PCSK9 were measured.The levels of RLP-C(low:RLP-C≤157 mg/L;high:RLP-C>157 mg/L)and PCSK9(low:PCSK9≤135.87μg/L;high:PCSK9>135.87μg/L)were represented using quartiles.Subjects were categorized into 4 groups according to their RLP-C and PCSK9 levels:Q4,high levels of RLP-C with high levels of PCSK9;Q3,high levels of RLP-C with low levels of PCSK9;Q2,low levels of RLP-C with high levels of PCSK9;and Q1,low levels of RLP-C with low levels of PCSK9.The association of RLP-C with MACEs in subjects with different PCSK9 levels was evaluated.Results::After a median follow-up of 9.5 years,1,325 subjects were included in the study and a total of 191 MACEs had occurred.The incidence of MACEs was higher in the RLP-C>157 mg/L group than the RLP-C≤157 mg/L group(18.40%vs.10.42%).Cox proportional hazards regression model analysis showed that increased RLP-C levels were associated with an increased risk of MACEs(hazard ratio:1.405;95%confidence interval:1.005-1.964;P<0.005).The incidence of MACEs was higher in the high RLP-C/PCSK9 group vs.the low RLP-C/PCSK9 group(20.68%vs.8.76%).Cox proportional hazards regression model analysis showed that RLP-C was associated with an increased risk of MACEs in subjects with high PCSK9 levels independent of traditional risk factors(hazard ratio:1.791;95%confidence interval:1.168-2.825;P=0.001),but not in those with low PCSK9 levels.Conclusions::RLP-C was identified as a risk factor for MACEs,particularly in subjects with high PCSK9 levels.Lowering PCSK9 levels may reduce residual risk in subjects with elevated plasma RLP-C levels.展开更多
基金This study was supported by the National Natural Science Foundation of China （No. 30500209 and 30973159） and Program for New Century Excellent Talents in University （No. NCET-06-0684）.
文摘Background Remnant-like lipoproteins （RLPs） have been demonstrated to accelerate the onset of endothelial progenitor cells （EPCs） senescence. Recent study has determined that microRNAs （miRNAs） were closely associated with cellular proliferation and senescence. This study aimed to examine whether RLPs lead to an alteration of miRNAs in senescent EPCs. Methods RLPs were prepared from plasma samples with immunoaffinity method. After 8 days of culture, EPCs were identified by flow cytometry analysis. Cells were incubated with RLPs for 72 hours. The senescent markers p161NK4a and senescence-associated beta-galactosidase （SA-^-gal） were detected by Western blotting analysis and 13-gal staining assay, respectively. A human miRNA microarray containing 723 miRNAs was used to detect the expression profile of miRNAs in control and senescent EPCs. The result from the above microarray was qualified by RT-PCR assay. Results RLPs dose-dependently up-regulated the protein level of p16INK4a in EPCs, and RLPs at a concentration of 100 pg/ml induced a significant increase in the percentage of SA-i3-gal-positive EPCs. Of 723 miRNAs, four miRNAs expressed differentially and significantly in RLPs-treated EPCs （P 〈0.05）, then their changes in expression were validated by real-time RT-PCR. Among them miR-148b and miR-155 were upregulated while miR-574-3p was down-regulated significantly when compared with control （P 〈0.01）. Conclusions RLPs result in the onset of EPCs senescence. Senescent EPCs induced by RLPs exhibit a different profile of miRNAs. These three miR-148b and miR-155 and miR-574-3p reach a significant difference when compared with control, indicating that microRNA might take part in RLPs-induced EPCs senescence.
基金supported by the National Key Research and Development Program of China (2021YFC2500604)to Li Sheng.
文摘Objective::The purpose of this study was to determine the relationship between remnant-like particle cholesterol(RLP-C)and major adverse cardiovascular events(MACEs)in patients with different levels of proprotein convertase subtilisin/kexin 9(PCSK9).Methods::From September 2007 to January 2009,1,859 subjects in Pingguoyuan communities in Beijing were initially screened.After excluding those with bedridden status,mental illness,severe systemic diseases,and missing data,1,680 subjects were recruited for follow up.All recruited subjects were followed up from February 2013 to September 2013(181 subjects were lost to follow-up)and from June 2017 to September 2018(174 subjects were lost to follow up).Finally,1,325 subjects were included in the study.General demographic characteristics,lifestyle and behaviors,disease history and use of medication was collected.Levels of total cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,fast blood glucose,RLP-C,low-density lipoprotein triglycerides and PCSK9 were measured.The levels of RLP-C(low:RLP-C≤157 mg/L;high:RLP-C>157 mg/L)and PCSK9(low:PCSK9≤135.87μg/L;high:PCSK9>135.87μg/L)were represented using quartiles.Subjects were categorized into 4 groups according to their RLP-C and PCSK9 levels:Q4,high levels of RLP-C with high levels of PCSK9;Q3,high levels of RLP-C with low levels of PCSK9;Q2,low levels of RLP-C with high levels of PCSK9;and Q1,low levels of RLP-C with low levels of PCSK9.The association of RLP-C with MACEs in subjects with different PCSK9 levels was evaluated.Results::After a median follow-up of 9.5 years,1,325 subjects were included in the study and a total of 191 MACEs had occurred.The incidence of MACEs was higher in the RLP-C>157 mg/L group than the RLP-C≤157 mg/L group(18.40%vs.10.42%).Cox proportional hazards regression model analysis showed that increased RLP-C levels were associated with an increased risk of MACEs(hazard ratio:1.405;95%confidence interval:1.005-1.964;P<0.005).The incidence of MACEs was higher in the high RLP-C/PCSK9 group vs.the low RLP-C/PCSK9 group(20.68%vs.8.76%).Cox proportional hazards regression model analysis showed that RLP-C was associated with an increased risk of MACEs in subjects with high PCSK9 levels independent of traditional risk factors(hazard ratio:1.791;95%confidence interval:1.168-2.825;P=0.001),but not in those with low PCSK9 levels.Conclusions::RLP-C was identified as a risk factor for MACEs,particularly in subjects with high PCSK9 levels.Lowering PCSK9 levels may reduce residual risk in subjects with elevated plasma RLP-C levels.
