The sodium-glucose co-transporter 2 inhibitor, empagliflozin, attenuates pulmonary vascular remodelling by inhibiting the phosphorylation of PDGF receptor-β.
Abstract
BACKGROUND AND PURPOSE: Pulmonary vascular remodelling is the key pathological feature of pulmonary arterial hypertension (PAH), but treatments targeting this process are lacking. Recent studies suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors, particularly empagliflozin, may improve PAH outcomes, although the underlying mechanisms remain largely unexplored.
EXPERIMENTAL APPROACH: PAH models were induced in Sprague-Dawley rats with monocrotaline or SU5416-hypoxia (SU-Hx), and empagliflozin (10 mg kg-1 day-1) or saline was administered orally. At the end point, haemodynamic, electrocardiographic parameters and pulmonary vascular remodelling were evaluated to investigate effects of empagliflozin in vivo. Effects of empagliflozin in vitro, were assessed using PDGF-BB-/hypoxia-induced proliferation and migration assays on human pulmonary arterial smooth muscle cells (PASMCs). Network pharmacology, molecular docking and surface plasmon resonance (SPR) were performed to explore potential mechanism(s) of empagliflozin treatment.
KEY RESULTS: Empagliflozin improved haemodynamic, electrocardiographic parameters and pulmonary vascular remodelling in monocrotaline-/SU-Hx-induced PAH models. Empagliflozin inhibited PDGF-BB/hypoxia-stimulated proliferation and migration of human PASMCs and arrested cells in the G0/G1 phase in a concentration-dependent manner. Network pharmacology, biological and SPR results suggested that empagliflozin ameliorated PAH by suppressing…
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.