Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education, FuWai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China.
Biochem Biophys Res Commun. 2010 Jul 23;398(2):212-6. doi: 10.1016/j.bbrc.2010.06.062. Epub 2010 Jun 18.
Angiopoietin-2 has been reported to regulate the inflammation process, which is associated with recurrence of stroke. The purpose of this study was to test the hypothesis that plasma levels of angiopoietin-2 and variants of angiopoietin-2 will confer risk of stroke recurrence. The association of plasma angiopoietin-2 (determined by using ELISA) and the variants in angiopoietin-2 promoter with stroke recurrence was tested in 1735 patients with stroke of three subtypes, lacunar infarct (n=475), atherothrombotic (n=794) and hemorrhage (n=466), for a period of following-up 4.5 years (mean), the association was evaluated by using Kaplan-Meier analysis and the Cox regression models. We found that angiopoietin-2 levels were associated with risk of stroke recurrence in lacunar infarct patients. Taking the lowest quartile as reference, the adjusted hazard ratio (HR) and 95% confidence intervals (CI) for stroke recurrence was 1.48 (0.74-2.95) for the second quartile, 2.56 (1.35-4.86) for the third and 2.15 (1.11-4.17) for the fourth. Allele T of rs3739391 in angiopoietin-2 promoter was associated with elevated angiopoietin-2 levels and increased risk of stroke recurrence in patients with lacunar infarct with HR 1.67 (1.06-2.63) relative to the allele C, but neither in those with atherothrombotic nor in those with hemorrhagic stroke. Our results indicate that both angiopoietin-2 and allele T of rs3739391 might be the risk marker for stroke recurrence in the patients with lacunar infarction. These findings may help to improve future prevention or therapy strategies for stroke. Even some conventional risk factors have been identified responsible for stroke recurrence, but these factors could not fully explain all the recurrent stroke events. Our study opens a new page for the first time that angiopoietin/tie2 pathway has a potential role in lacunar stroke recurrence. Since several strategies are available for blocking or neutralizing plasma angiopoietin-2, especially eicosapentaenoic acid rich in sea food. Our finding obviously has its clinical implication if it was proved by large, prospective clinical studies.
血管生成素-2 已被报道可调节炎症过程，而炎症过程与中风复发有关。本研究旨在检验血浆血管生成素-2 水平及其变体是否会增加中风复发风险的假说。通过 ELISA 测定血浆血管生成素-2（angiopoeitin-2）水平及血管生成素-2 启动子的变体，对 1735 例三种亚型中风患者（腔隙性梗死[lacunar infarct]475 例，动脉粥样硬化血栓性[atherothrombotic]794 例，出血性[hemorrhagic]466 例）进行了为期 4.5 年的随访，通过 Kaplan-Meier 分析和 Cox 回归模型评估其与中风复发的相关性。我们发现血管生成素-2 水平与腔隙性梗死患者的中风复发风险相关。以最低四分位数为参考，第二四分位数、第三四分位数和第四四分位数的中风复发调整后的危险比（hazard ratio，HR）和 95%置信区间（confidence intervals，CI）分别为 1.48（0.74-2.95）、2.56（1.35-4.86）和 2.15（1.11-4.17）。血管生成素-2 启动子 rs3739391 的 T 等位基因与升高的血管生成素-2 水平相关，并增加了腔隙性梗死患者的中风复发风险，与 C 等位基因相比 HR 为 1.67（1.06-2.63），但在动脉粥样硬化血栓性或出血性中风患者中无此相关性。我们的结果表明，血管生成素-2 和 rs3739391 的 T 等位基因可能是腔隙性梗死患者中风复发的风险标志物。这些发现可能有助于改善未来中风的预防或治疗策略。尽管已经确定了一些传统的危险因素与中风复发有关，但这些因素并不能完全解释所有的复发性中风事件。我们的研究首次表明，血管生成素/ Tie2 通路在腔隙性卒中复发中可能具有潜在作用。由于有几种策略可用于阻断或中和血浆血管生成素-2，尤其是富含海鲜的二十碳五烯酸。如果这一发现能被大型前瞻性临床研究证实，那么它显然具有临床意义。
