2. Academic Validation
  3. Cardiac Microvascular Endothelial Enhancement of Cardiomyocyte Function Is Impaired by Inflammation and Restored by Empagliflozin

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

  • JACC Basic Transl Sci. 2019 Sep 4;4(5):575-591. doi: 10.1016/j.jacbts.2019.04.003.
Rio P Juni 1,  Diederik W D Kuster 1,  Max Goebel 1,  Michiel Helmes 1 2,  René J P Musters 1,  Jolanda van der Velden 1 3,  Pieter Koolwijk 1,  Walter J Paulus 1,  Victor W M van Hinsbergh 1 3
Affiliations

Affiliations

  • 1 Amsterdam Cardiovascular Sciences, Department of Physiology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
  • 2 CytoCypher B.V., Wageningen, the Netherlands.
  • 3 Netherlands Heart Institute, Utrecht, the Netherlands.
PMID: 31768475 DOI: 10.1016/j.jacbts.2019.04.003
Abstract

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.

Keywords

CM, cardiomyocyte; CMEC, cardiac microvascular endothelial cell; Ca, calcium; DM, diabetes mellitus; DPPH, 1,1-diphenyl-picrylhydrazyl; EC, endothelial cell; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; JNK, Jun N-terminal kinase; L-NAME, N(ω)-nitro-L-arginine methyl ester; LV, left ventricular; NK-κB, nuclear factor-κB; NO, nitric oxide; ROS, reactive oxygen species; SGLT2, sodium glucose transporter 2; contraction and relaxation; eNOS, endothelial nitric oxide synthase; empagliflozin; endothelial cell–derived nitric oxide; heart failure; oxidative stress.

Figures
Products