Canagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces lung fibrosis in left heart dysfunction.

Publication/Presentation Date

7-3-2025

Abstract

BackgroundLeft heart failure is the most common cause of pulmonary hypertension and increases morbidity and mortality. We investigate the use of canagliflozin, an antidiabetic Sodium-glucose Cotransporter-2 Inhibitor, which is first-line therapy in congestive heart failure, on pulmonary fibrosis in a porcine model of chronic myocardial ischemia.MethodologySixteen Yorkshire swine, eight in a normal diet control arm (NDC) and eight in the canagliflozin arm (CAN), underwent left thoracotomy and ameroid constrictor placement on the left circumflex artery. Seven weeks after placement, the swine underwent harvest procedure. During harvest, left ventricular contractility was quantified by direct left ventricular pressure-volume loops. Protein expression was quantified by immunoblotting and Masson's trichrome staining was utilized to assess perivascular collagen deposition.ResultsAnalysis of left ventricular ejection fraction demonstrated no significant difference between CAN and NDC. Western blot analysis demonstrated increases in TGFβ signaling pathways with decreased free TGFβ and TGFβ monomers in CAN pigs (

First Page

2184923251352222

Last Page

2184923251352222

ISSN

1816-5370

Disciplines

Medicine and Health Sciences

PubMedID

40605641

Department(s)

Fellows and Residents, Department of Surgery

Document Type

Article

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