Cohen Elad, Aviram Michael, Khatib Soliman, Rabin Asaf, Mannheim Dalit, Karmeli Ron, Vaya Jacob
Oxidative Stress Research Laboratory, Migal-Galilee Technology Center and Tel Hai College, P.O. Box 831, Kiryat Shmona 11016, Israel.
J Lipids. 2012;2012:762560. doi: 10.1155/2012/762560. Epub 2012 May 29.
Human carotid plaque components interact directly with circulating blood elements and thus they might affect each other. We determined plaque paraoxonase1 (PON1) hydrolytic-catalytic activity and compared plaque and blood levels of lipids, HDL, PON1, and HbA1c, as well as plaque-oxidized lipids in symptomatic and asymptomatic patients. Human carotid plaques were obtained from symptomatic and asymptomatic patients undergoing routine endarterectomy, and the lesions were ground and extracted for PON activity and lipid content determinations. Plaque PONs preserved paraoxonase, arylesterase, and lactonase activities. The PON1-specific inhibitor 2-hydroxyquinoline almost completely inhibited paraoxonase and lactonase activities, while only moderately inhibiting arylesterase activity. Oxysterol and triglyceride levels in plaques from symptomatic and asymptomatic patients did not differ significantly, but plaques from symptomatic patients had significantly higher (135%) linoleic acid hydroperoxide (LA-13OOH) levels. Their serum PON1 activity, cholesterol and triglyceride levels did not differ significantly, but symptomatic patients had significantly lower (28%) serum HDL levels and higher (18%) HbA1c levels. Thus LA-13OOH, a major atherogenic plaque element, showed significant negative correlations with serum PON1 activity and HDL levels, and a positive correlation with the prodiabetic atherogenic HbA1c. Plaque PON1 retains its activity and may decrease plaque atherogenicity by reducing specific oxidized lipids (e.g., LA-13OOH). The inverse correlation between plaque LA-13OOH level and serum HDL level and PON1 activity suggests a role for serum HDL and PON1 in LA-13OOH accumulation.
人类颈动脉斑块成分与循环血液成分直接相互作用，因此它们可能相互影响。我们测定了斑块对氧磷酶1（PON1）的水解催化活性，并比较了有症状和无症状患者斑块及血液中的脂质、高密度脂蛋白（HDL）、PON1和糖化血红蛋白（HbA1c）水平，以及斑块氧化脂质水平。从接受常规动脉内膜切除术的有症状和无症状患者中获取人类颈动脉斑块，将病变组织研磨并提取，用于测定PON活性和脂质含量。斑块中的PON保留了对氧磷酶、芳基酯酶和内酯酶活性。PON1特异性抑制剂2-羟基喹啉几乎完全抑制对氧磷酶和内酯酶活性，而仅适度抑制芳基酯酶活性。有症状和无症状患者斑块中的氧化甾醇和甘油三酯水平无显著差异，但有症状患者的斑块中亚油酸氢过氧化物（LA-13OOH）水平显著更高（高135%）。他们的血清PON1活性、胆固醇和甘油三酯水平无显著差异，但有症状患者的血清HDL水平显著更低（低28%），HbA1c水平更高（高18%）。因此，LA-13OOH作为主要的致动脉粥样硬化斑块成分，与血清PON1活性和HDL水平呈显著负相关，与促糖尿病的致动脉粥样硬化HbA1c呈正相关。斑块PON1保留其活性，并可能通过减少特定的氧化脂质（如LA-13OOH）来降低斑块的致动脉粥样硬化性。斑块LA-13OOH水平与血清HDL水平和PON1活性之间的负相关表明血清HDL和PON1在LA-13OOH积累中起作用。
