Empagliflozin prevents doxorubicin-induced myocardial dysfunction

Autor: Alberto Polimeni, Masakazu Yasuda, Chiara Mignogna, Laura Tammè, Salvatore De Rosa, Carmen Spaccarotella, Jolanda Sabatino, Ciro Indolfi, Claudio Iaconetti, Sabato Sorrentino, Andrea Amorosi
Přispěvatelé: Sabatino, J., De Rosa, S., Tamme, L., Iaconetti, C., Sorrentino, S., Polimeni, A., Mignogna, C., Amorosi, A., Spaccarotella, C., Yasuda, M., Indolfi, C.
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
lcsh:Diseases of the circulatory (Cardiovascular) system
Fibrosi
Endocrinology
Diabetes and Metabolism
Cardiotoxicity
Heart failure
Left ventricular function
Animals
Benzhydryl Compounds
Cardiomyopathies
Diastole
Disease Models
Animal
Extracellular Signal-Regulated MAP Kinases
Fibrosis
Glucosides
Mice
Inbred C57BL
Myocytes
Cardiac
Sodium-Glucose Transporter 2 Inhibitors
Systole
Ventricular Dysfunction
Left
Ventricular Function
Left
Ventricular Remodeling
Doxorubicin
Left
Cardiomyopathy
030204 cardiovascular system & hematology
Inbred C57BL
Mice
0302 clinical medicine
Ventricular Dysfunction
polycyclic compounds
Ventricular Function
Original Investigation
Benzhydryl Compound
Sodium-Glucose Transporter 2 Inhibitor
Standard treatment
Furosemide
030220 oncology & carcinogenesis
Cardiology
Cardiology and Cardiovascular Medicine
Cardiac
medicine.drug
medicine.medical_specialty
Glucoside
03 medical and health sciences
Internal medicine
medicine
Empagliflozin
Cardiomyopathie
Myocytes
Extracellular Signal-Regulated MAP Kinase
Animal
business.industry
medicine.disease
Blood pressure
lcsh:RC666-701
Disease Models
business
Mace
Zdroj: Cardiovascular Diabetology, Vol 19, Iss 1, Pp 1-11 (2020)
Cardiovascular Diabetology
ISSN: 1475-2840
DOI: 10.1186/s12933-020-01040-5
Popis: Background Empagliflozin showed efficacy in controlling glycaemia, leading to reductions in HbA1c levels, weight loss and blood pressure, compared to standard treatment. Moreover, the EMPA-REG OUTCOME trial demonstrated a 14% reduction of major adverse cardiovascular events (MACE), a 38% reduction in cardiovascular (CV) death and a 35% reduction in the hospitalization rate for heart failure (HF). These beneficial effect on HF were apparently independent from glucose control. However, no mechanistic in vivo studies are available to explain these results, yet. We aimed to determine the effect of empagliflozin on left ventricular (LV) function in a mouse model of doxorubicin-induced cardiomyopathy (DOX-HF). Methods Male C57Bl/6 mice were randomly assigned to the following groups: controls (CTRL, n = 7), doxorubicin (DOX, n = 14), DOX plus empagliflozin (DOX + EMPA, n = 14), or DOX plus furosemide (DOX + FURO group, n = 7). DOX was injected intraperitoneally. LV function was evaluated at baseline and after 6 weeks of treatment using high-resolution echocardiography with 2D speckle tracking (Vevo 2100). Histological assessment was obtained using Haematoxylin and Eosin and Masson’s Goldner staining. Results A significant decrease in both systolic and diastolic LV function was observed after 6 weeks of treatment with doxorubicin. EF dropped by 32% (p = 0.002), while the LS was reduced by 42% (p Conclusion Empagliflozin attenuates the cardiotoxic effects exerted by doxorubicin on LV function and remodelling in nondiabetic mice, independently of glycaemic control. These findings support the design of clinical studies to assess their relevance in a clinical setting.
Databáze: OpenAIRE
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