Abstract
BackgroundMyocardial 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.MethodsFourteen 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.ResultsBaseline 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).Conclusion/interpretationEmpagliflozin 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.
Highlights
Coronary artery occlusion results in myocardial infarction (MI), myocardial necrosis and subsequent fibrosis, often resulting in decreased cardiac function and heart failure
Cardiac structure and function were typical of healthy young rats, i.e., somewhat smaller areas of the AP level vs. the papillary muscle (PM) level attributing for the conical shape of the left ventricular (LV) (Table 1)
The AP level is the cardiac territory mostly affected by MI, and we describe relevant changes of echocardiography at both levels, distinctively
Summary
Coronary artery occlusion results in myocardial infarction (MI), myocardial necrosis and subsequent fibrosis, often resulting in decreased cardiac function and heart failure. The main post-MI pathway leading to heart failure involves extensive negative left ventricular (LV) remodeling, caused by cardiomyocytes’ death and their replacement with a non-functioning fibrotic tissue. Daud et al Cardiovasc Diabetol (2021) 20:132 process They express high levels of procollagens that enhance collagen deposition in the newly developed scar [7]. Deposition of extracellular proteins, the cornerstone of fibrosis, is a combined and multistep process, involving, pro-inflammatory cytokines such as TGF-β1 and its down-stream effector Smad3 [8, 9]. Myocardial fibrosis is a multistep process, which results in collagen deposition in the injured muscle. Little is known on the effects of empagliflozin in non-diabetic patients early post myocardial infarction
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