Internal Medicine, Division of Nephrology and Hypertension, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
J Hypertens. 2021 Jan;39(1):12-22. doi: 10.1097/HJH.0000000000002591.
: Although considerable success has been shown for antihypertensive medications, the resistant hypertension and hypertension-related organ damages are still the important clinical issues and pose as high health and economic pressure. Therefore, novel therapeutic techniques and antihypertensive drugs are needed to advance more effective therapy of hypertension and hypertension-related disease to ameliorate mortality and healthcare costs worldwide. In this review, we highlight the latest progress in supporting the therapeutic potential of Elabela (ELA), a recently discovered early endogenous ligand for G-protein-coupled receptor apelin peptide jejunum, apelin receptor. Systemic administration of ELA exerts vasodilatory, antihypertensive, cardioprotective, and renoprotective effects, whereas central application of ELA increases blood pressure and causes cardiovascular remodeling primarily secondary to the hypertension. In addition, ELA drives extravillous trophoblast differentiation and prevents the pathogenesis of preeclampsia (a gestational hypertensive syndrome) by promoting placental angiogenesis. These findings strongly suggest peripheral ELA's therapeutic potential in preventing and treating hypertension and hypertension-related diseases including cardiovascular disease, kidney disease, and preeclampsia. Since therapeutic use of ELA is mainly limited by its short half-life and parenteral administration, it may be a clinical application candidate for the therapy of hypertension and its complications when fused with a large inert chemicals (e.g. polyethylene glycol, termed polyethylene glycol-ELA-21) or other proteins (e.g. the Fc fragment of IgG and albumin, termed Fc-ELA-21 or albumin-ELA-21), and new delivery methods are encouraged to develop to improve the efficacy of ELA fragments on apelin peptide jejunum or alternative unknown receptors.
尽管降压药物取得了相当大的成功，但抗高血压药物和与高血压相关的器官损伤仍然是重要的临床问题，给健康和经济带来了巨大压力。因此，需要新的治疗技术和降压药物来推进更有效的高血压和高血压相关疾病的治疗，以改善全球的死亡率和医疗保健成本。在这篇综述中，我们强调了支持 Elabela（ELA）治疗潜力的最新进展，ELA 是一种最近发现的 G 蛋白偶联受体 apelin 肽回肠的内源性配体，apelin 受体。ELA 的全身给药具有血管扩张、降压、心脏保护和肾脏保护作用，而 ELA 的中枢给药会升高血压并导致心血管重塑，主要是继发性高血压。此外，ELA 可促进绒毛外滋养层细胞分化，并通过促进胎盘血管生成来预防子痫前期（妊娠期高血压综合征）的发病机制。这些发现强烈表明，外周 ELA 具有预防和治疗高血压和高血压相关疾病（包括心血管疾病、肾脏疾病和子痫前期）的治疗潜力。由于 ELA 的治疗用途主要受到其半衰期短和需要通过注射给药的限制，因此当与惰性较大的化学物质（例如聚乙二醇，称为聚乙二醇-ELA-21）或其他蛋白质（例如 IgG 的 Fc 片段和白蛋白，称为 Fc-ELA-21 或白蛋白-ELA-21）融合时，它可能成为治疗高血压及其并发症的临床应用候选物，并鼓励开发新的给药方法来提高 ELA 片段对 apelin 肽回肠或替代未知受体的疗效。
