RT Journal Article
SR Electronic
T1 Empagliflozin Improves the MicroRNA Signature of Endothelial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Diabetes
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 116
OP 122
DO 10.1124/jpet.121.001251
VO 384
IS 1
A1 Mone, Pasquale
A1 Lombardi, Angela
A1 Kansakar, Urna
A1 Varzideh, Fahimeh
A1 Jankauskas, Stanislovas S.
A1 Pansini, Antonella
A1 Marzocco, Stefania
A1 De Gennaro, Stefano
A1 Famiglietti, Michele
A1 Macina, Gaetano
A1 Frullone, Salvatore
A1 Santulli, Gaetano
YR 2023
UL http://jpet.aspetjournals.org/content/384/1/116.abstract
AB Endothelial dysfunction represents a key mechanism underlying heart failure with preserved ejection fraction (HFpEF), diabetes mellitus (DM), and frailty. However, reliable biomarkers to monitor endothelial dysfunction in these patients are lacking. In this study, we evaluated the expression of a panel of circulating microRNAs (miRs) involved in the regulation of endothelial function in a population of frail older adults with HFpEF and DM treated for 3 months with empagliflozin, metformin, or insulin. We identified a distinctive pattern of miRs that were significantly regulated in HFpEF patients compared to healthy controls and to HFpEF patients treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin. Three miRs were significantly downregulated (miR-126, miR-342-3p, and miR-638) and two were significantly upregulated (miR-21 and miR-92) in HFpEF patients compared to healthy controls. Strikingly, two of these miRs (miR-21 and miR-92) were significantly reduced in HFpEF patients after the 3-month treatment with empagliflozin, whereas no significant differences in the profile of endothelial miRs were detected in patients treated with metformin or insulin. Taken together, our findings demonstrate for the first time that specific circulating miRs involved in the regulation of endothelial function are significantly regulated in frail HFpEF patients with DM and in response to SGLT2 inhibition.SIGNIFICANCE STATEMENT We have identified a novel microRNA signature functionally involved in the regulation of endothelial function that is significantly regulated in frail patients with HFpEF and diabetes. Moreover, the treatment with the SGLT2 inhibitor empagliflozin caused a modification of some of these microRNAs in a direction that was opposite to what observed in HFpEF patients, indicating a rescue of endothelial function. Our findings are relevant for clinical practice inasmuch as we were able to establish novel biomarkers of disease and response to therapy.