Objective: Because the lipoprotein effects of statin and fibric acid derivativ es therapies differ, we studied the effects of these therapies in patients with hyperlipidemia on lipoproteins, vasomotor function, and pl...Objective: Because the lipoprotein effects of statin and fibric acid derivativ es therapies differ, we studied the effects of these therapies in patients with hyperlipidemia on lipoproteins, vasomotor function, and plaque stability. Method s: We administered simvastatin, 20 mg daily, to 27 patients with hypercholestero lemia and coronary artery disease, or fenofibrate, 200 mg daily, to 27 patients with pure hypertriglyceridemia during 8 weeks. Results: As expected, simvastatin significantly lowered total cholesterol and low density lipoprotein cholestero l (LDL C) more, and fenofibrate decreased triglyceride and increased high dens ity lipoprotein cholesterol(HDL C) more than either therapy. Simvastatin and fe nofibrate significantly improved the percent flow mediated dilator response to hyperemia by 183±41%and by 30±7%, respectively (each P< 0.001); however, sim vastatin significantly improved more (P< 0.001). Simvastatin and fenofibrate sig nificantly lowered plasma levels of tumor necrosis factor alpha (TNF α) by 13 ±4%and by 10±4%, respectively (P=0.009 and P=0.006, respectively) with a sim ilar degree(P=0.614). Simvastatin significantly reduced plasma levels of total M MP-9 and TIMP-1 more(P=0.005 and P=0.036, respectively), compared with fenofib rate showing no reduction. There were significant correlations between the degre e of changes in TNF-αand the degree of changes in MMP-9 activity (r=0.376, P= 0.053). Conclusions: Simvastatin and fenofibrate demonstrated antiatheroscleroti c effects via different mechanisms.展开更多
背景:血管性血友病因子水解蛋白酶13(a disintegrin and metalloproteinase with a thrombospondin type 1motif,member 13,ADAMTS13)可结合并酶切血管性血友病因子,在防止血小板过多聚集和血栓的形成中起到关键作用。重组ADAMTS13通常...背景:血管性血友病因子水解蛋白酶13(a disintegrin and metalloproteinase with a thrombospondin type 1motif,member 13,ADAMTS13)可结合并酶切血管性血友病因子,在防止血小板过多聚集和血栓的形成中起到关键作用。重组ADAMTS13通常选择在真核细胞中表达分泌,然而对于其表达纯化目前仍缺乏一个明确高效的途径。目的:寻找合适的宿主细胞,得到稳定表达野生型ADAMTS13和功能增强型ADAMTS13的细胞株,建立高纯度ADAMTS13的纯化方法,进而研究其生物学功能。方法:以野生型ADAMTS13重组质粒为模板,利用位点突变试剂盒得到功能增强型ADAMTS13重组质粒。比较CHO-S细胞、CHO-K1细胞、293T细胞对ADAMTS13的表达效果,挑选出合适的宿主细胞。通过Ni柱亲和层析和分子筛纯化蛋白;采用7.5%SDS-PAGE、Western-blot鉴定野生型ADAMTS13和功能增强型ADAMTS13的纯度及特异性;利用原子力显微镜技术检测野生型及功能增强型ADAMTS13与血管性血友病因子A2的相互作用,鉴定两种蛋白的活性。结果与结论:相对于CHO-S和CHO-K1,293T细胞更适合作为野生型ADAMTS13和功能增强型ADAMTS13的表达宿主;经Ni柱亲和层析和分子筛纯化后,所得到的野生型ADAMTS13和功能增强型ADAMTS13质量浓度分别为103.7,149.7 mg/L,且两种蛋白纯度均约90%;原子力显微镜检测结果显示,野生型ADAMTS13、功能增强型ADAMTS13与血管性血友病因子A2的黏附频率分别为11.37%,14.70%,表明功能增强型ADAMTS13与血管性血友病因子A2的结合亲和力更高,这与近期ADAMTS13构象研究一致。展开更多
文摘Objective: Because the lipoprotein effects of statin and fibric acid derivativ es therapies differ, we studied the effects of these therapies in patients with hyperlipidemia on lipoproteins, vasomotor function, and plaque stability. Method s: We administered simvastatin, 20 mg daily, to 27 patients with hypercholestero lemia and coronary artery disease, or fenofibrate, 200 mg daily, to 27 patients with pure hypertriglyceridemia during 8 weeks. Results: As expected, simvastatin significantly lowered total cholesterol and low density lipoprotein cholestero l (LDL C) more, and fenofibrate decreased triglyceride and increased high dens ity lipoprotein cholesterol(HDL C) more than either therapy. Simvastatin and fe nofibrate significantly improved the percent flow mediated dilator response to hyperemia by 183±41%and by 30±7%, respectively (each P< 0.001); however, sim vastatin significantly improved more (P< 0.001). Simvastatin and fenofibrate sig nificantly lowered plasma levels of tumor necrosis factor alpha (TNF α) by 13 ±4%and by 10±4%, respectively (P=0.009 and P=0.006, respectively) with a sim ilar degree(P=0.614). Simvastatin significantly reduced plasma levels of total M MP-9 and TIMP-1 more(P=0.005 and P=0.036, respectively), compared with fenofib rate showing no reduction. There were significant correlations between the degre e of changes in TNF-αand the degree of changes in MMP-9 activity (r=0.376, P= 0.053). Conclusions: Simvastatin and fenofibrate demonstrated antiatheroscleroti c effects via different mechanisms.
文摘背景:血管性血友病因子水解蛋白酶13(a disintegrin and metalloproteinase with a thrombospondin type 1motif,member 13,ADAMTS13)可结合并酶切血管性血友病因子,在防止血小板过多聚集和血栓的形成中起到关键作用。重组ADAMTS13通常选择在真核细胞中表达分泌,然而对于其表达纯化目前仍缺乏一个明确高效的途径。目的:寻找合适的宿主细胞,得到稳定表达野生型ADAMTS13和功能增强型ADAMTS13的细胞株,建立高纯度ADAMTS13的纯化方法,进而研究其生物学功能。方法:以野生型ADAMTS13重组质粒为模板,利用位点突变试剂盒得到功能增强型ADAMTS13重组质粒。比较CHO-S细胞、CHO-K1细胞、293T细胞对ADAMTS13的表达效果,挑选出合适的宿主细胞。通过Ni柱亲和层析和分子筛纯化蛋白;采用7.5%SDS-PAGE、Western-blot鉴定野生型ADAMTS13和功能增强型ADAMTS13的纯度及特异性;利用原子力显微镜技术检测野生型及功能增强型ADAMTS13与血管性血友病因子A2的相互作用,鉴定两种蛋白的活性。结果与结论:相对于CHO-S和CHO-K1,293T细胞更适合作为野生型ADAMTS13和功能增强型ADAMTS13的表达宿主;经Ni柱亲和层析和分子筛纯化后,所得到的野生型ADAMTS13和功能增强型ADAMTS13质量浓度分别为103.7,149.7 mg/L,且两种蛋白纯度均约90%;原子力显微镜检测结果显示,野生型ADAMTS13、功能增强型ADAMTS13与血管性血友病因子A2的黏附频率分别为11.37%,14.70%,表明功能增强型ADAMTS13与血管性血友病因子A2的结合亲和力更高,这与近期ADAMTS13构象研究一致。
