Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.
Neurosci Biobehav Rev. 2017 Mar;74(Pt B):342-355. doi: 10.1016/j.neubiorev.2016.06.015. Epub 2016 Jun 23.
The postural tachycardia syndrome (POTS) is characterised clinically by symptoms of light-headedness, palpitations, fatigue and exercise intolerance occurring with standing and relieved by lying down. Symptoms occur in association with an inappropriate rise in heart rate in the absence of a fall in blood pressure with the assumption of standing. The pathophysiology of POTS is complicated and poorly understood. Plasma norepinephrine (NE) is often elevated in patients with POTS, resulting in consideration of dysfunction of the norepinephrine transporter (NET) encoded by SLC6A2 gene. Whilst some studies have implicated a defect in the SLC6A2 gene, the cause of reduced SLC6A2 expression and function remains unclear. The search to explain the molecular mechanism of NET dysfunction has focused on genetic variation in the SLC6A2 gene and remains inconclusive. More recent studies show epigenetic mechanisms implicated in the regulation of SLC6A2 expression. In this article, we discuss the epigenetic mechanisms involved in SLC6A2 repression and highlight the potential therapeutic application of targeting these mechanisms in POTS.
体位性心动过速综合征（POTS）的临床特征是直立时出现头晕、心悸、疲劳和运动不耐受等症状，躺下后缓解。这些症状与站立时心率不适当升高有关，而血压无下降。POTS 的病理生理学很复杂，目前了解甚少。体位性心动过速综合征患者的血浆去甲肾上腺素（NE）通常升高，导致考虑去甲肾上腺素转运蛋白（NET）功能障碍，其由 SLC6A2 基因编码。虽然一些研究表明 SLC6A2 基因存在缺陷，但 SLC6A2 表达和功能降低的原因仍不清楚。解释 NET 功能障碍的分子机制的研究重点是 SLC6A2 基因的遗传变异，但尚无定论。最近的研究表明，参与 SLC6A2 表达调控的表观遗传机制。在本文中，我们讨论了 SLC6A2 抑制相关的表观遗传机制，并强调了针对这些机制治疗 POTS 的潜在应用。
