Miwa Yoshikazu, Oda Hiroshi, Shiina Yasuhiko, Shikata Kentaro, Tsushima Motoo, Nakano Satomi, Maruyama Taro, Kyotani Shingo, Eguchi Naomi, Urade Yoshihiro, Takahashi-Yanaga Fumi, Morimoto Sachio, Sasaguri Toshiyuki
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hypertens Res. 2008 Oct;31(10):1931-9. doi: 10.1291/hypres.31.1931.
Recent studies suggest that lipocalin-type prostaglandin (PG) D synthase (L-PGDS), which converts PGH2 to PGD2, is implicated in the pathogenesis of atherosclerosis. However, clinical evidence for the association between serum L-PGDS levels and atherosclerosis has not been reported. In this study, we measured the serum L-PGDS concentration using sandwich enzyme-linked immunosorbent assay (ELISA) and investigated the association with traditional cardiovascular risk factors and surrogate atherosclerotic indices, such as the maximum score of the intima-media complex thickness of the carotid artery (C-IMT(max)) and the brachial-ankle pulse wave velocity (ba-PWV), in 500 non-treated asymptomatic subjects. The serum concentration of L-PGDS was 0.56+/-0.01 (mean+/-SEM, range 0.25-1.27, median 0.54) mg/L. Serum L-PGDS levels increased with age and were higher in men than in women. Serum L-PGDS was higher in subjects with hypertension and increased with increasing numbers of the traditional atherosclerotic risk factors. When the subjects were divided into four groups according to the levels of serum L-PGDS, the age-adjusted values of C-IMT(max) and ba-PWV were significantly increased in subjects with higher serum L-PGDS levels (quartile 3 and quartile 4) compared to those in the lowest quartile (quartile 1), for both genders. Multiple regression analysis including risk factors revealed that serum L-PGDS was an independent determinant for ba-PWV (beta=0.130, p<0.001). Serum L-PGDS tended to associate with C-IMT(max) but was not statistically significant (beta=0.084, p=0.075). In conclusion, our results suggest that an increase in serum L-PGDS concentration is associated with the progression of atherosclerosis.
近期研究表明，将前列腺素（PG）H2转化为PGD2的脂质运载蛋白型前列腺素D合酶（L-PGDS）与动脉粥样硬化的发病机制有关。然而，血清L-PGDS水平与动脉粥样硬化之间关联的临床证据尚未见报道。在本研究中，我们采用夹心酶联免疫吸附测定法（ELISA）测量了500例未经治疗的无症状受试者的血清L-PGDS浓度，并研究了其与传统心血管危险因素及替代动脉粥样硬化指标的关联，这些指标包括颈动脉内膜中层复合体厚度的最大值（C-IMT(max)）和臂踝脉搏波速度（ba-PWV）。血清L-PGDS浓度为0.56±0.01（平均值±标准误，范围0.25 - 1.27，中位数0.54）mg/L。血清L-PGDS水平随年龄增长而升高，男性高于女性。高血压患者的血清L-PGDS水平更高，且随着传统动脉粥样硬化危险因素数量的增加而升高。当根据血清L-PGDS水平将受试者分为四组时，与最低四分位数（四分位数1）的受试者相比，血清L-PGDS水平较高（四分位数3和四分位数4）的受试者中，无论男女，年龄校正后的C-IMT(max)和ba-PWV值均显著升高。包括危险因素的多元回归分析显示，血清L-PGDS是ba-PWV的独立决定因素（β = 0.130，p < 0.001）。血清L-PGDS倾向于与C-IMT(max)相关，但无统计学意义（β = 0.084，p = 0.075）。总之，我们的结果表明血清L-PGDS浓度升高与动脉粥样硬化的进展有关。
