Kawaguchi A, Miyao Y, Noguchi T, Nonogi H, Yamagishi M, Miyatake K, Kamikubo Y, Kumeda K, Tsushima M, Yamamoto A, Kato H
National Cardiovascular Center Research Institute, Osaka, Japan.
Arterioscler Thromb Vasc Biol. 2000 Jan;20(1):251-8. doi: 10.1161/01.atv.20.1.251.
To elucidate the distribution and clinical implications of tissue factor pathway inhibitor (TFPI) concentrations, we measured TFPI levels consisting of preheparin free, lipoprotein-bound (Lp-bound), and endothelial cell-anchor pools in 156 patients with coronary artery disease (average age, 61.2+/-9.1 years; range, 32 to 78 years) by heparin infusion (50 IU/kg) and compared them with the preheparin TFPI levels of 229 healthy subjects (average age, 59. 6+/-9.4 years; range, 41 to 80 years). The patients had lower preheparin free TFPI and lower HDL cholesterol (HDL-C) levels than the healthy subjects with equivalent Lp-bound forms (free TFPI, 15. 9+/-6.5 versus 19.2+/-8.1 ng/mL). In a partial correlation analysis, the preheparin free TFPI levels were shown to be inversely correlated with the HDL-C concentrations in both the patients (r=-0. 454, P<0.001) and the healthy subjects (r=-0.136, P<0.05). As determined by comparison of preheparin and postheparin plasma, the patients generally showed preheparin free TFPI <10%, Lp-bound TFPI at 30%, and endothelial cell-anchor TFPI at 60%. When the patients were divided into 4 categories by their LDL cholesterol (LDL-C, 130 mg/dL) and HDL-C (40 mg/dL) levels to specify their coronary risks, the low-HDL-C groups had significantly increased preheparin and postheparin free TFPI levels and decreased postheparin LPL levels, whereas the high-LDL-C groups showed increased levels of Lp-bound TFPI. In a partial correlation analysis, we found a proportional relation between postheparin free TFPI and apolipoprotein A-II (r=0. 5327) and between HDL-C and LPL (r=0.4906), whereas postheparin free TFPI was inversely correlated with HDL-C (r=-0.4280) and postheparin LPL (r=-0.4791). The inverse relationship between TFPI and LPL suggests that increased free TFPI concentrations as a compensatory response of the endothelium to prevent atherothrombotic processes compete with and displace LPL on endothelial surface, resulting in reduced LPL and low HDL-C.
为了阐明组织因子途径抑制剂（TFPI）浓度的分布及其临床意义，我们通过静脉输注肝素（50IU/kg），检测了156例冠心病患者（平均年龄61.2±9.1岁；范围32至78岁）中由游离前肝素、脂蛋白结合型（Lp结合型）和内皮细胞锚定型组成的TFPI水平，并将其与229例健康受试者（平均年龄59.6±9.4岁；范围41至80岁）的游离前肝素TFPI水平进行比较。这些患者的游离前肝素TFPI和高密度脂蛋白胆固醇（HDL-C）水平低于具有同等Lp结合形式的健康受试者（游离TFPI：15.9±6.5对19.2±8.1ng/mL）。在偏相关分析中，游离前肝素TFPI水平在患者（r=-0.454，P<0.001）和健康受试者（r=-0.136，P<0.05）中均与HDL-C浓度呈负相关。通过比较游离前肝素和肝素化后血浆发现，患者通常表现为游离前肝素TFPI<10%，Lp结合型TFPI为30%，内皮细胞锚定型TFPI为60%。当根据患者的低密度脂蛋白胆固醇（LDL-C，130mg/dL）和HDL-C（40mg/dL）水平将其分为4类以明确其冠心病风险时，低HDL-C组的游离前肝素和肝素化后游离TFPI水平显著升高，肝素化后脂蛋白脂肪酶（LPL）水平降低，而高LDL-C组的Lp结合型TFPI水平升高。在偏相关分析中，我们发现肝素化后游离TFPI与载脂蛋白A-II之间存在比例关系（r=0.5327），HDL-C与LPL之间也存在比例关系（r=0.4906），而肝素化后游离TFPI与HDL-C呈负相关（r=-0.4280），与肝素化后LPL呈负相关（r=-0.4791）。TFPI与LPL之间的负相关关系表明，作为内皮细胞预防动脉粥样硬化血栓形成过程的一种代偿反应，游离TFPI浓度升高会与内皮表面的LPL竞争并取代LPL，导致LPL减少和HDL-C降低。
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