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.
目的:探讨极短期氟伐他汀治疗对2型糖尿病患者餐后血浆可溶性 P-选择素和纤溶酶原激活物抑制剂1(PAI-1)抗原浓度的影响。方法:40例初诊2型糖尿病患者和20例健康人(健康对照组)在禁食12 h 后接受高脂餐,检测空腹和餐后4 h 血浆PAI-1抗原、可溶性 P-选择索和血脂水平。2型糖尿病患者被随机分为两组,分别接受安慰剂(安慰剂组,n=20)和氟伐他汀40 mg/d(氟伐他汀组,n=20)治疗。1周后,再次进行高脂餐负荷试验。结果:两组2型糖尿病患者治疗前及治疗1周后和健康对照组餐后4 h 较本组同期空腹血浆甘油三酯(TG)浓度比均有显著升高(P<0.05);两组2型糖尿病患者治疗前餐后4 h 血浆 TG 浓度显著高于健康对照组(P<0.05)。两组2型糖尿病患者治疗前及安慰剂组治疗1周后餐后4 h 血浆可溶性 P-选择素、PAI-1抗原浓度均较本组同期空腹显著升高(P 均<0.05),均有显著性差异;而氟伐他汀组治疗1周后和健康对照组无显著变化。将治疗前的两组2型糖尿病患者和健康对照组作为一个整体(n=60)进行相关分析,结果显示:餐后4 h 血浆 TG 浓度分别与餐后血浆可溶性 P-选择素、PAI-1抗原浓度显著正相关。治疗1周后,两组2型糖尿病患者的血脂、血糖水平较治疗前均无显著变化。结论:一次性高脂餐导致2型糖尿病患者餐后纤溶功能异常和血管炎症。极短期的氟伐他汀治疗可减轻这种餐后改变。
