首页> 外文期刊>Prostaglandins, Leukotrienes, and Essential Fatty Acids >The low-density lipoprotein (LDL)-associated PAF-acetylhydrolase activity and the extent of LDL oxidation are important determinants of the autoantibody titers against oxidized LDL in patients with coronary artery disease.
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The low-density lipoprotein (LDL)-associated PAF-acetylhydrolase activity and the extent of LDL oxidation are important determinants of the autoantibody titers against oxidized LDL in patients with coronary artery disease.

机译:低密度脂蛋白(LDL)相关的PAF-乙酰水解酶活性和LDL氧化程度是确定冠心病患者抗氧化LDL的自身抗体滴度的重要决定因素。

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The oxidation of low-density lipoprotein (LDL) induces immunogenic epitopes, many of which are due to oxidatively modified phospholipids (oxPL). Lysophosphatidylcholine (lyso-PC) which is generated during LDL oxidation through the hydrolysis of oxPL by LDL-associated PAF-acetylhydrolase (PAF-AH) is also immunogenic. We investigated whether the LDL-associated PAF-AH and the extent of LDL oxidation influence the autoantibody titers against oxidized LDL (oxLDL) in patients with stable angina as well as in apparently healthy volunteers. Three types of copper-oxidized LDL, were prepared at the end of the lag, propagation or decomposition phase (oxLDL(L), oxLDL(P) and oxLDL(D), respectively). Similar types of oxidized LDL were prepared after previous inactivation of endogenous PAF-AH [oxLDL(-)]. All these types of oxLDL as well as malondialdehyde-modified LDL (MDA-LDL) were used as antigens. Antibody titers against the above antigens were measured with an ELISA method in the serum of 65 patients with stable angina and 47 apparently healthy volunteers. Both groups exhibited higher autoantibody titers against each type of oxLDL(-) compared to the respective type of oxLDL (P<0.00001). In both groups autoantibody titers were higher when the oxLDL(P) and oxLDL(D) or oxLDL(-)(P) and oxLDL(-)(D) were used as antigens compared to oxLDL(L) (P<0.04) or to oxLDL(-)(L), respectively (P<0.0001 for all comparisons). Patients had significantly higher titers against all types of oxLDL (enriched in lyso-PC) and oxLDL(-) (enriched in intact oxPL) compared to controls. Autoantibody titers against MDA-LDL did not differ between patients and controls. Multivariate logistic regression analysis showed that among the autoantibody titers measured only those towards oxLDL(P) are associated with a significantly higher risk for coronary artery disease. LDL-associated PAF-AH activity may play an important role in decreasing the overall immunogenicity of oxLDL, whereas the extent of LDL oxidation seems to modulate the epitopes formed on oxLDL. Lyso-PC, a major component of oxLDL(P), could be mainly responsible for the elevated autoantibody titers against oxLDL in patients with stable angina.
机译:低密度脂蛋白(LDL)的氧化诱导了免疫原性表位,其中许多是由于氧化修饰的磷脂(oxPL)引起的。在LDL氧化过程中,通过LDL相关的PAF-乙酰水解酶(PAF-AH)水解oxPL产生的溶血磷脂酰胆碱(lyso-PC)也具有免疫原性。我们调查了LDL相关的PAF-AH和LDL氧化程度是否影响稳定型心绞痛患者以及明显健康的志愿者对氧化LDL(oxLDL)的自身抗体滴度。在滞后,传播或分解阶段结束时分别准备了三种类型的铜氧化LDL(分别为oxLDL(L),oxLDL(P)和oxLDL(D))。先前内源性PAF-AH [oxLDL(-)]失活后,制备了类似类型的氧化LDL。所有这些类型的oxLDL以及丙二醛修饰的LDL(MDA-LDL)都被用作抗原。用ELISA法在65名稳定型心绞痛患者和47名显然健康的志愿者的血清中测定了针对上述抗原的抗体效价。与每种类型的oxLDL相比,两组针对每种oxLDL(-)均显示出更高的自身抗体滴度(P <0.00001)。与oxLDL(L)相比,使用oxLDL(P)和oxLDL(D)或oxLDL(-)(P)和oxLDL(-)(D)作为抗原时,两组的自身抗体滴度均较高(P <0.04)或分别为oxLDL(-)(L)(对于所有比较,P <0.0001)。与对照相比,患者对所有类型的oxLDL(富含溶血PC)和oxLDL(-)(富含完整oxPL)的滴度明显更高。患者和对照之间针对MDA-LDL的自身抗体滴度没有差异。多元逻辑回归分析表明,在测得的自身抗体滴度中,仅针对oxLDL(P)的滴度与冠心病的风险显着相关。 LDL相关的PAF-AH活性可能在降低oxLDL的整体免疫原性中起重要作用,而LDL的氧化程度似乎调节oxLDL上形成的表位。 Lyso-PC是oxLDL(P)的主要成分,可能主要负责稳定型心绞痛患者对oxLDL的自身抗体滴度升高。

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