Division of Cardiac Surgery, St. Michael's Hospital, Toronto, ON, Canada.
Division of Cardiac Surgery, St. Michael's Hospital, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Biochem Biophys Res Commun. 2020 Mar 26;524(1):50-56. doi: 10.1016/j.bbrc.2020.01.015. Epub 2020 Jan 21.
Pulmonary arterial hypertension (PAH) is a rare, but progressive and devastating vascular disease with few treatment options to prevent the advancement to right ventricular dysfunction hypertrophy and failure. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, enhances urinary glucose excretion as well as reduces cardiovascular events and mortality in individuals with type 2 diabetes. While empagliflozin has been reported to lower systemic hypertension due to increased diuresis, the effect of empagliflozin on PAH is unknown. We used monocrotaline (MCT)-treated Sprague-Dawley rats to determine if empagliflozin alters PAH-associated outcomes. Compared to vehicle control, daily empagliflozin administration significantly improved survival in rats with severe MCT-induced PAH. Hemodynamic assessments showed that empagliflozin treatment significantly reduced mean pulmonary artery pressure, right ventricular systolic pressure, and increased pulmonary acceleration time. Empagliflozin treatment resulted in reduced right ventricular hypertrophy and fibrosis. Histological and molecular assessments of lung vasculature revealed significantly reduced medial wall thickening and decreased muscularization of pulmonary arterioles after empagliflozin treatment compared to vehicle-treated rats. In summary, SGLT2 inhibition with empagliflozin lowered mortality, reduced right ventricle systolic pressure, and attenuated maladaptive pulmonary remodeling in MCT-induced PAH. Clinical studies evaluating the efficacy of SGLT-2 inhibition should be considered for patients with PAH.
肺动脉高压（PAH）是一种罕见的进行性和破坏性血管疾病，治疗选择有限，无法预防右心室功能障碍、肥厚和衰竭的进展。恩格列净是一种钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂，可增强尿糖排泄，并降低 2 型糖尿病患者的心血管事件和死亡率。虽然已有报道称恩格列净通过增加利尿作用降低系统性高血压，但恩格列净对 PAH 的影响尚不清楚。我们使用野百合碱（MCT）处理的 Sprague-Dawley 大鼠来确定恩格列净是否改变 PAH 相关结局。与载体对照相比，每日给予恩格列净可显著提高严重 MCT 诱导的 PAH 大鼠的生存率。血流动力学评估显示，恩格列净治疗可显著降低平均肺动脉压、右心室收缩压，并增加肺动脉加速度时间。恩格列净治疗可减少右心室肥厚和纤维化。对肺血管的组织学和分子评估显示，与接受载体治疗的大鼠相比，恩格列净治疗后肺小动脉中层壁增厚明显减少，肌化程度降低。总之，SGLT2 抑制剂恩格列净降低了死亡率，降低了右心室收缩压，并减轻了 MCT 诱导的 PAH 中的适应性肺重构。应考虑对 PAH 患者进行 SGLT-2 抑制的临床研究。
