Diabetic cardiomyopathy: the need for adjusting experimental models to meet clinical reality
Por:
Lezoualc'h, F, Badimon, L, Baker, H, Bernard, M, Czibik, G, De Boer, RA, D'Humieres, T, Kergoat, M, Kowala, M, Rieusset, J, Vilahur, G, Detrait, M, Watson, C, Derumeaux, GA
Publicada:
22 may 2023
Ahead of Print:
1 sep 2022
Resumen:
Diabetic cardiomyopathy (CM), occurring in the absence of hypertension, coronary artery disease, and valvular or congenital heart disease, is now recognized as a distinct, multifactorial disease leading to ventricular hypertrophy and abnormal myocardial contractility that correlates with an array of complex molecular and cellular changes. Animal models provide the unique opportunity to investigate mechanistic aspects of diabetic CM, but important caveats exist when extrapolating findings obtained from preclinical models of diabetes to humans. Indeed, animal models do not recapitulate the complexity of environmental factors, most notably the duration of the exposure to insulin resistance that may play a crucial role in the development of diabetic CM. Moreover, most preclinical studies are performed in animals with uncontrolled or poorly controlled diabetes, whereas patients tend to undergo therapeutic intervention. Finally, whilst type 2 diabetes mellitus prevalence trajectory mainly increases at 40- < 75 years (with a currently alarming increase at younger ages, however), it is a legitimate concern how closely rodent models employing young animals recapitulate the disease developing in old people. The aim of this review is to identify the current limitations of rodent models and to discuss how future mechanistic and preclinical studies should integrate key confounding factors to better mimic the diabetic CM phenotype.
Filiaciones:
Lezoualc'h, F:
Univ Paul Sabatier, INSERM, Inst Malad Metab & Cardiovasc, UMR 1297,I2MC, 1 Ave Jean Poulhes,BP 84225, F-31432 Toulouse 4, France
Badimon, L:
IR Hosp Santa Creu & St Pau, CiberCV, IISantPau, Cardiovasc Program ICCC, C St Antoni Maria Claret 167, Barcelona 08025, Spain
Baker, H:
Eli Lilly & Co, Lilly Res Labs, Diabet & Complicat Res, 307 E Merrill St, Indianapolis, IN 46225 USA
Bernard, M:
Aix Marseille Univ, Fac Med, CRMBM, CNRS, 27 Bd Jean Moulin, F-13385 Marseille, France
Czibik, G:
Univ Paris Est Creteil UPEC, Henri Mondor Hosp, AP HP,Fac Sante Creteil, FHU SENEC,Dept Physiol,INSERM U955, 8 Rue Gen Sarrail, F-94010 Creteil, France
De Boer, RA:
Univ Med Ctr Groningen, Dept Cardiol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands
D'Humieres, T:
Univ Paris Est Creteil UPEC, Henri Mondor Hosp, AP HP,Fac Sante Creteil, FHU SENEC,Dept Physiol,INSERM U955, 8 Rue Gen Sarrail, F-94010 Creteil, France
Kergoat, M:
Metabrain Res, 19 Av Prof Cadiot, F-94700 Maisons Alfort, France
Kowala, M:
Indiana Biosci Res Inst, 1210 Waterway Blvd Ste 2000, Indianapolis, IN 46202 USA
Rieusset, J:
Univ Claude Bernard Lyon1, UMR INSERM U1060, INRA U1397, Lab CarMeN, Batiment CENS ELI-2D,165 Chemin Grand Revoyet, F-69310 Pierre Benite, France
Vilahur, G:
IR Hosp Santa Creu & St Pau, CiberCV, IISantPau, Cardiovasc Program ICCC, C St Antoni Maria Claret 167, Barcelona 08025, Spain
Detrait, M:
Univ Paul Sabatier, INSERM, Inst Malad Metab & Cardiovasc, UMR 1297,I2MC, 1 Ave Jean Poulhes,BP 84225, F-31432 Toulouse 4, France
Watson, C:
Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland
Derumeaux, GA:
Univ Paris Est Creteil UPEC, Henri Mondor Hosp, AP HP,Fac Sante Creteil, FHU SENEC,Dept Physiol,INSERM U955, 8 Rue Gen Sarrail, F-94010 Creteil, France
Green Submitted, Green Accepted, Green
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