Cardiac Microvascular Endothelial Enhancement of Cardiomyocyte Function Is Impaired by Inflammation and Restored by Empagliflozin

Rio P. Juni, Diederik W. D. Kuster, Max Goebel, Michiel Helmes, René J. P. Musters, Jolanda van der Velden, Pieter Koolwijk, Walter J. Paulus, Victor W. M. van Hinsbergh

Research output: Contribution to journalArticleAcademicpeer-review

116 Citations (Scopus)


The positive findings of the EMPA-REG OUTCOME trial (Randomized, Placebo-Controlled Cardiovascular Outcome Trial of Empagliflozin) on heart failure (HF) outcome in patients with type 2 diabetes mellitus suggest a direct effect of empagliflozin on the heart. These patients frequently have HF with preserved ejection fraction (HFpEF), in which a metabolic risk-related pro-inflammatory state induces cardiac microvascular endothelial cell (CMEC) dysfunction with subsequent cardiomyocyte (CM) contractility impairment. This study showed that CMECs confer a direct positive effect on contraction and relaxation of CMs, an effect that requires nitric oxide, is diminished after CMEC stimulation with tumor necrosis factor-α, and is restored by empagliflozin. Our findings on the effect of empagliflozin on CMEC-mediated preservation of CM function suggests that empagliflozin can be used to treat the cardiac mechanical implications of microvascular dysfunction in HFpEF.
Original languageEnglish
Pages (from-to)575-591
JournalJACC. Basic to translational science
Issue number5
Publication statusPublished - 1 Sept 2019

Cite this