Hypertension：基因表达的变化可致孕妇高血压

凝血恶烷合酶(Credit: Image courtesy of Virginia Commonwealth University)

近日，弗吉尼亚联邦大学医学院的研究者通过研究发现，关键酶基因表达的变化在子癫前期的怀孕妇女中可以促使高血压以及增加血块成型的敏感性。这项研究发现可以为临床上治疗孕妇高血压以及血块成型敏感性提供一些治疗线索，血块形成敏感可以阻塞血流进而导致孕妇各项内脏器官衰竭。

研究者研究从分子水平揭示了孕妇先兆子癫的原因，而且识别出表观遗传机制或许在起作用。表观遗传学涉及基因表达的改变，而不是DNA序列的改变。这项研究结果刊登在了国际杂志Hypertension上，研究小组报道了凝血恶烷合酶，一种重要的炎症酶，这种酶在子癫前期的孕妇血液中明显升高，编码该酶的基因也参与了很多疾病的形成，比如心血管病和中风，这种酶可以引起凝血的发生，进而增加血压促使血块形成。

“当前的研究为先兆子癫相关的表观遗传学成因提出了新的观点，而且，这也是第一项研究揭示了母体血管中表观遗传学的改变和先兆子癫有关。”研究者Scott W.Walsh表示。Walsh还说，主要的表观遗传机制是DNA的甲基化，可以控制基因的表达，血管中酶量的增加和DNA甲基化的降低直接相关，而且中性白细胞可以深入血管中，中性白细胞是帮助机体抵抗感染的白血细胞。

研究者Walsh指出，未来潜在的治疗孕妇先兆子癫的方法包括抑制凝血恶烷合酶、堵塞血栓烷受体或者在饮食中补充叶酸，叶酸的补充可以增加甲基供体以保护DNA甲基化的反向改变，从而影响凝血恶烷合酶的表达。这项研究基于研究者前期的研究，在研究者前期研究中，研究者揭示了中性白细胞作为孕妇先兆子癫的致病因子的角色。这项研究由国立健康中心支持。（生物谷：T.Shen编译）

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doi:10.1161/​HYPERTENSIONAHA.111.188730
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Reduced Methylation of the Thromboxane Synthase Gene Is Correlated With Its Increased Vascular Expression in Preeclampsia

Ahmad A. Mousa, Jerome F. Strauss III, Scott W. Walsh

Preeclampsia is characterized by increased thromboxane and decreased prostacyclin levels, which predate symptoms, and can explain some of the clinical manifestations of preeclampsia, including hypertension and thrombosis. In this study, we examined DNA methylation of the promoter region of the thromboxane synthase gene (TBXAS1) and the expression of thromboxane synthase in systemic blood vessels of normal pregnant and preeclamptic women. Thromboxane synthase is responsible for the synthesis of thromboxane A2, a potent vasoconstrictor and activator of platelets. We also examined the effect of experimentally induced DNA hypomethylation on the expression of thromboxane synthase in a neutrophil-like cell line (HL-60 cells) and in cultured vascular smooth muscle and endothelial cells. We found that DNA methylation of the TBXAS1 promoter was decreased and thromboxane synthase expression was increased in omental arteries of preeclamptic women as compared with normal pregnant women. Increased thromboxane synthase expression was observed in vascular smooth muscles cells, endothelial cells, and infiltrating neutrophils. Experimentally induced DNA hypomethylation only increased expression of thromboxane synthase in the neutrophil-like cell line, whereas tumor necrosis factor-α, a neutrophil product, increased its expression in cultured vascular smooth muscle cells. Our study suggests that epigenetic mechanisms and release of tumor necrosis factor-α by infiltrating neutrophils could contribute to the increased expression of thromboxane synthase in maternal systemic blood vessels, contributing to the hypertension and coagulation abnormalities associated with preeclampsia.