Highlights
- •Sodiumglucose cotransporter 2 inhibitors (SGLT2i) improved pulmonary hypertension.
- •SGLT2i inhibited pulmonary arterial remodeling in left heart disease.
- •SGLT2i inhibited pulmonary artery smooth muscle cells migration.
Abstract
Background
Group 2 pulmonary hypertension (PH) represents PH caused by left heart disease (PH-LHD).
LHD induces left-sided filling and PH, finally leading to pulmonary vascular remodeling.
Tofogliflozin (TOFO) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used in
the treatment of diabetes. Recent studies have shown that SGLT2 inhibitors have beneficial
effects on heart failure, but the effects of SGLT2 inhibitors on PH-LHD remain unclear.
We hypothesized that TOFO has protective effects against pulmonary vascular remodeling
in PH-LHD mice.
Methods
We generated two murine models of PH-LHD: a transverse aortic constriction (TAC) model;
and a high-fat diet (HFD) model. C57BL/6J mice were subjected to TAC and treated with
TOFO (3 mg/kg/day) for 3 weeks. AKR/J mice were fed HFD and treated with TOFO (3 mg/kg/day)
for 20 weeks. We then measured physical data and right ventricular systolic pressure
(RVSP) and performed cardiography. Human pulmonary artery smooth muscle cells (PASMCs)
were cultured and treated with TOFO.
Results
Mice treated with TOFO demonstrated increased urine glucose levels. TAC induced left
ventricular hypertrophy and increased RVSP. TOFO treatment improved RVSP. HFD increased
body weight (BW) and RVSP compared with the normal chow group. TOFO treatment ameliorated
increases in BW and RVSP induced by HFD. Moreover, PASMCs treated with TOFO showed
suppressed migration.
Conclusions
TOFO treatment ameliorated right heart overload and pulmonary vascular remodeling
for PH-LHD models, suggesting that SGLT2 inhibitors are effective for treating PH-LHD.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: October 28, 2022
Accepted:
September 27,
2022
Received in revised form:
September 21,
2022
Received:
June 17,
2022
Identification
Copyright
© 2022 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
