Empagliflozin Improves Mitochondrial Biogenesis and Ameliorates Experimental Pulmonary Vascular Remodeling, But May Not Benefit Patients with Pulmonary Arterial Hypertension
Abstract
Abstract Background The sodium glucose cotransporter 2 (SGLT2) inhibitor may improve mitochondrial biogenesis and attenuate pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). We investigated the impact of empagliflozin in PAH. Methods Lung sections and primary cell cultures isolated from microvascular endothelial cells (MVECs) were collected from control subjects and PAH patients. MVECs were treated with empagliflozin and mitochondrial biogenesis, cell metabolism, oxidative stress and cell proliferation were evaluated. Subsequently, PAH was induced in male and female rats (n=12 respectively) with SU5416 injection (25 mg/kg s.c.) followed by 3 weeks of hypoxia (10% O 2 ), the experimental PAH model known to mimic human PAH pathophysiology. Four weeks after SU5416 injection, rats were treated by empagliflozin (300 mg/kg chow, n=12) or placebo (n=12) for 4 weeks and hemodynamic, protein and histological analyses were performed. In addition, we conducted a phase IIa proof of concept trial, EMPHOWER, to assess the feasibility of 12 weeks of empagliflozin treatment in PAH patients. Results Immunofluorescent staining of human lung tissue showed expression of SGLT2 in the intima of small pulmonary arteries from PAH patients, not controls. In comparison to control MVECs, PAH MVECs showed increased protein expression of SGLT2, along with decreased expression of the peroxisome proliferator-activated receptor gamma coactivator-1α. Furthermore, empagliflozin enhanced…
Read the paper
Related studies
- Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol
- Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
- SGLT2 Inhibitors in Heart Failure: Targeted Metabolomics and Energetic Metabolism
- Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Sodium-glucose cotransporter inhibitors: beyond glycaemic control
- Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.