Mazor Rafi, Shurtz-Swirski Revital, Farah Raymond, Kristal Batya, Shapiro Galina, Dorlechter Faina, Cohen-Mazor Meital, Meilin Edna, Tamara Snitkovski, Sela Shifra
Eliachar Research Laboratory, Western Galilee Hospital, Nahariya, Israel.
Atherosclerosis. 2008 Apr;197(2):937-43. doi: 10.1016/j.atherosclerosis.2007.08.014. Epub 2007 Sep 17.
Oxidative stress (OS) and chronic inflammation are involved and contribute to the development of atherosclerosis. Primed polymorphonuclear leukocytes (PMNLs) are a possible source for superoxide radicals and inflammatory mediators, hence can promote OS and inflammation. The involvement of primed PMNLs in clinical states associated with high risk for developing cardiovascular disease and atherosclerosis, such as hypertension, renal failure and diabetes has been described, however, little is known about PMNLs characteristics in hyperlipidemic patients.
Hyperlipidemic patients and healthy control (HC) subjects were enrolled in this cross-sectional study. PMNL priming was estimated by measuring the rate of superoxide release and by levels of membrane CD11b. PMNL priming and myeloperoxidase (MPO) levels served as OS indices. Inflammation was linked to peripheral white blood cells and PMNL counts and to apoptosis. Systemic inflammation was estimated by blood levels of fibrinogen, C-reactive protein (CRP), transferrin and albumin. PMNL priming and inflammation parameters were related to the severity of hyperlipidemia.
PMNLs from hyperlipidemic patients are primed compared to HC. A decrease in PMNL-MPO levels with increased levels of serum MPO were found in hyperlipidemic patients. Leukocyte counts tended to be higher in hyperlipidemic patients with increased PMNL apoptosis. PMNL priming and fibrinogen levels correlated positively with the severity of hyperlipidemia (r=0.32, P=0.02 for CD11b vs. cholesterol and r=0.38, P=0.009 for CD11b vs. LDL-c; r=0.35, P=0.01 for fibrinogen vs. cholesterol and r=0.3, P=0.03 for superoxide release vs. LDL-c).
PMNLs are primed in hyperlipidemic patients contributing to OS and inflammation in these patients. This study highlights primed PMNLs as an additional risk factor for promoting atherosclerosis in hyperlipidemic patients.
氧化应激（OS）和慢性炎症参与并促成动脉粥样硬化的发展。预激活的多形核白细胞（PMNLs）是超氧自由基和炎症介质的一个可能来源，因此可促进氧化应激和炎症。已描述了预激活的PMNLs参与与心血管疾病和动脉粥样硬化高风险相关的临床状态，如高血压、肾衰竭和糖尿病，然而，对于高脂血症患者中PMNLs的特征知之甚少。
高脂血症患者和健康对照（HC）受试者被纳入这项横断面研究。通过测量超氧释放速率和膜CD11b水平来评估PMNL预激活。PMNL预激活和髓过氧化物酶（MPO）水平作为氧化应激指标。炎症与外周白细胞和PMNL计数以及细胞凋亡相关。通过纤维蛋白原、C反应蛋白（CRP）、转铁蛋白和白蛋白的血水平评估全身炎症。PMNL预激活和炎症参数与高脂血症的严重程度相关。
与HC相比，高脂血症患者的PMNLs被预激活。在高脂血症患者中发现随着血清MPO水平升高，PMNL-MPO水平降低。PMNL凋亡增加的高脂血症患者白细胞计数往往更高。PMNL预激活和纤维蛋白原水平与高脂血症的严重程度呈正相关（CD11b与胆固醇相比，r = 0.32，P = 0.02；CD11b与低密度脂蛋白胆固醇相比，r = 0.38, P = 0.009；纤维蛋白原与胆固醇相比，r = 0.35, P = 0.01；超氧释放与低密度脂蛋白胆固醇相比，r = 0.3, P = 0.03）。
高脂血症患者的PMNLs被预激活，导致这些患者发生氧化应激和炎症。本研究强调预激活的PMNLs是高脂血症患者促进动脉粥样硬化的一个额外危险因素。
