The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats

• Published in: Cardiovascular diabetology Vol. 20; no. 1; p. 132
• Main Authors: Daud, Elias, Ertracht, Offir, Bandel, Nadav, Moady, Gassan, Shehadeh, Monah, Reuveni, Tali, Atar, Shaul
• Format: Journal Article
• Language: English
• Published: England BioMed Central 02-07-2021; BMC
• Subjects: Animals; Benzhydryl Compounds - pharmacology; Cardiac function; Cardiac muscle; Cardiomyocytes; Cardiovascular diseases; Catheters; Collagen; Collagen - metabolism; Collagen deposition; Diabetes; Diabetes mellitus; Disease Models, Animal; Drug dosages; Echocardiography; Empagliflozin; Experiments; Fibrosis; Glucose; Glucosides - pharmacology; Heart attacks; Heart failure; Hemodynamics; Histology; Hydroxyproline; Hydroxyproline - metabolism; Laboratory animals; Male; Myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardium - metabolism; Myocardium - pathology; Na+/glucose cotransporter; Original Investigation; Ostomy; Physiology; Rats; Rats, Sprague-Dawley; Scars; Smad3 protein; Smad3 Protein - metabolism; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Software; Stroke Volume - drug effects; TGF-β1/Smad3 pathway; Time Factors; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Veins & arteries; Ventricular Function, Left - drug effects; United States > US; Japan; Myocardial infarction; TGF-β1/Smad3 pathway; Empagliflozin; Collagen deposition; Fibrosis
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-021-01322-6

Myocardial fibrosis is a multistep process, which results in collagen deposition in the injured muscle. Empagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), decreases cardiovascular events risk. Little is known on the effects of empagliflozin in non-diabetic patients early post myocardial infarction.
Fourteen non-diabetic rats underwent myocardial infarction induction, and treated or not (control)immediately after myocardial infarction by daily empagliflozin (30 mg/kg/day). We evaluated cardiac function at baseline, 2 and 4 weeks after myocardial infarction by echocardiography, and prior to sacrifice by Millar pressure-volume system. We performed histological and biochemical evaluation of fibrosis and humoral factors promoting fibrosis.
Baseline ejection fractions were 69.9 ± 5.3% and 76.4 ± 5.4%, and dropped to final values of 40.1 ± 5.8% and 39.4 ± 5.4% in the control and empagliflozin groups, respectively (P < 0.001 vs. baseline, P > 0.05 between groups). Collagen deposition, measured as collagen volume fraction, was higher in both the scar and the remote cardiac areas of the control group 79.1 ± 6.2% and 4.6 ± 2.5% for control, and 53.8 ± 5.4% and 2.5 ± 1.3% for empagliflozin group, respectively (P < 0.05 for each). Remote cardiac muscle collagen, measured by hydroxyproline, was 4.1 ± 0.4 μg/μl and 3.6 ± 0.2 μg/μl (P = 0.07). TGF-β1 and Smad3 expression decreased by empagliflozin-18.73 ± 16.32%, 9.16 ± 5.69% and 16.32 ± 5.4%, 7.00 ± 5.28% in the control and empagliflozin groups, respectively (P < 0.05).
Empagliflozin administered early after myocardial infarction reduce myocardial fibrosis and inhibit the TGF-β1/Smad3 fibrotic pathway, probably prior to exerting any hemodynamic or physiological effect.