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氧化磷脂、脂蛋白(a)及氧化型脂蛋白生物标志物在心脏性猝死及经皮血管重建成功后慢性闭塞冠状动脉中的作用

The role of oxidized phospholipids, lipoprotein (a) and biomarkers of oxidized lipoproteins in chronically occluded coronary arteries in sudden cardiac death and following successful percutaneous revascularization.

作者信息

Fefer Paul, Tsimikas Sotirios, Segev Amit, Sparkes John, Otsuka Fumiyuki, Kolodgie Frank, Virmani Renu, Juliano Joseph, Charron Thierry, Strauss Bradley H

机构信息

Schulich Heart Center, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada M4N 3M5.

出版信息

Cardiovasc Revasc Med. 2012 Jan-Feb;13(1):11-9. doi: 10.1016/j.carrev.2011.08.001. Epub 2011 Nov 13.

Abstract

AIMS

OxPL are pro-inflammatory and may mediate atherogenesis, thrombosis and endothelial dysfunction. We studied the histological presence and temporal increases in oxidized phospholipids on apolipoprotein B-100 particles (OxPL/apoB), lipoprotein (a) [Lp(a)] and biomarkers of oxidized lipoproteins in subjects with chronic total coronary occlusions (CTO) with sudden cardiac death (SCD) and following percutaneous coronary intervention (PCI).

METHODS

Eight subjects with SCD and CTO and 33 patients with successful PCI of CTO were included. Blood samples were drawn before PCI, immediately post-PCI, at 6 and 24 h, at 3 days and at 1 week. Plasma levels of OxPL/apoB, Lp(a), IgG and IgM autoantibodies to malondialdehyde (MDA) low-density lipoprotein and apoB-immune complexes were measured in all samples and compared with previous data from 141 patients undergoing PCI of non-CTO vessels.

RESULTS

Immunohistochemistry of coronary CTOs revealed OxPL and MDA-like epitopes, particularly in areas of recanalized and organized thrombus and neovascularization. Following PCI, OxPL/apoB and Lp(a) levels, expressed as percent change from baseline levels before PCI, rose gradually and progressively over the next 7 days. In contrast, levels of OxPL/apoB and Lp(a) in non-CTO vessels rose immediately post PCI and then dropped rapidly to baseline within 24 h.

CONCLUSIONS

CTOs contain immunohistological evidence of OxPL and MDA-like epitopes. Successful PCI of CTOs results in a slower increase in OxPL/apoB and Lp(a) but higher increase in IgM immune complexes compared to non-CTO vessels. Pro-inflammatory oxidation-specific epitopes may impact development of CTOs and affect outcomes following PCI that can be evaluated in larger clinical trials.

摘要

目的

氧化磷脂具有促炎作用,可能介导动脉粥样硬化、血栓形成和内皮功能障碍。我们研究了慢性冠状动脉完全闭塞(CTO)合并心源性猝死(SCD)以及接受经皮冠状动脉介入治疗(PCI)的患者载脂蛋白B - 100颗粒上氧化磷脂(OxPL/apoB)、脂蛋白(a)[Lp(a)]的组织学存在情况以及氧化磷脂生物标志物随时间的变化。

方法

纳入8例SCD合并CTO患者和33例CTO成功接受PCI治疗的患者。在PCI术前、术后即刻、术后6小时、24小时、3天和1周采集血样。检测所有样本中OxPL/apoB、Lp(a)、抗丙二醛(MDA)低密度脂蛋白IgG和IgM自身抗体以及载脂蛋白B免疫复合物的血浆水平,并与141例非CTO血管接受PCI治疗患者的既往数据进行比较。

结果

冠状动脉CTO的免疫组织化学显示存在OxPL和类MDA表位,特别是在再通和机化血栓以及新生血管形成区域。PCI术后,OxPL/apoB和Lp(a)水平以相对于PCI术前基线水平的百分比变化表示,在接下来的7天内逐渐且持续上升。相比之下,非CTO血管中OxPL/apoB和Lp(a)水平在PCI术后立即上升,然后在24小时内迅速降至基线。

结论

CTO含有OxPL和类MDA表位的免疫组织学证据。与非CTO血管相比,CTO成功PCI导致OxPL/apoB和Lp(a)升高较慢,但IgM免疫复合物升高较高。促炎氧化特异性表位可能影响CTO的发展并影响PCI后的结果,这可在更大规模的临床试验中进行评估。

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