Department of Internal Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA.
Int J Mol Sci. 2019 Jun 28;20(13):3182. doi: 10.3390/ijms20133182.
Regardless of the cause, symptomatic heart failure (HF) with reduced ejection fraction (rEF) is characterized by pathological activation of the renin-angiotensin-aldosterone system (RAAS) with sodium retention and extracellular fluid expansion (edema). Here, we review the role of active renin, a crucial, upstream enzymatic regulator of the RAAS, as a prognostic and diagnostic plasma biomarker of heart failure with reduced ejection fraction (HFrEF) progression; we also discuss its potential as a pharmacological bio-target in HF therapy. Clinical and experimental studies indicate that plasma renin activity is elevated with symptomatic HFrEF with edema in patients, as well as in companion animals and experimental models of HF. Plasma renin activity levels are also reported to be elevated in patients and animals with rEF before the development of symptomatic HF. Modulation of renin activity in experimental HF significantly reduces edema formation and the progression of systolic dysfunction and improves survival. Thus, specific assessment and targeting of elevated renin activity may enhance diagnostic and therapeutic precision to improve outcomes in appropriate patients with HFrEF.
无论病因如何,射血分数降低的有症状心力衰竭(HF)的特征是肾素-血管紧张素-醛固酮系统(RAAS)的病理性激活伴有钠潴留和细胞外液扩张(水肿)。在这里,我们回顾了活性肾素的作用,活性肾素是 RAAS 的关键上游酶调节因子,作为射血分数降低的心力衰竭(HFrEF)进展的预后和诊断血浆生物标志物;我们还讨论了它作为 HF 治疗中药理学生物靶点的潜力。临床和实验研究表明,在伴有水肿的有症状 HFrEF 患者以及伴侣动物和 HF 实验模型中,血浆肾素活性升高。在出现有症状 HF 之前,报告 rEF 患者和动物的血浆肾素活性水平也升高。在实验性 HF 中调节肾素活性可显著减少水肿形成和收缩功能障碍的进展,并提高生存率。因此,对升高的肾素活性进行特定评估和靶向可能会提高诊断和治疗的准确性,从而改善适当的 HFrEF 患者的预后。