Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy

Marino, Fabiola; Salerno, Nadia; Scalise, Mariangela; Salerno, Luca; Torella, Annalaura; Molinaro, Claudia; Chiefalo, Antonio; Filardo, Andrea; Siracusa, Chiara; Panuccio, Giuseppe; Ferravante, Carlo; Giurato, Giorgio; Rizzo, Francesca; Torella, Michele; Donniacuo, Maria; De Angelis, Antonella; Viglietto, Giuseppe; Urbanek, Konrad; Weisz, Alessandro; Torella, Daniele; Cianflone, Eleonora

doi:10.3390/ijms24021132

Open AccessArticle

Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy

by

Fabiola Marino

^1,†

,

Nadia Salerno

^2,†,

Mariangela Scalise

¹,

Luca Salerno

¹,

Annalaura Torella

³

,

Claudia Molinaro

²,

Antonio Chiefalo

¹,

Andrea Filardo

²,

Chiara Siracusa

²,

Giuseppe Panuccio

²,

Carlo Ferravante

⁴

,

Giorgio Giurato

⁴

,

Francesca Rizzo

⁴

,

Michele Torella

⁵,

Maria Donniacuo

⁶,

Antonella De Angelis

⁶,

Giuseppe Viglietto

¹,

Konrad Urbanek

⁷,

Alessandro Weisz

⁴

,

Daniele Torella

^1,*

and

Eleonora Cianflone

^2,*

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¹

Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy

²

Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy

³

Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy

⁴

Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana′, University of Salerno, 84081 Salerno, Italy

⁵

Department of Translational Medical Science, University of Campania “L. Vanvitelli”, 80138 Naples, Italy

⁶

Department of Experimental Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy

⁷

Department of Molecular Medicine and Medical Biotechnology, Federico II University, 88121 Naples, Italy

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2023, 24(2), 1132; https://doi.org/10.3390/ijms24021132

Submission received: 21 December 2022 / Revised: 1 January 2023 / Accepted: 3 January 2023 / Published: 6 January 2023

(This article belongs to the Special Issue Effects of Dyslipidemia and Metabolic Syndrome on Cardiac and Vascular Dysfunction)

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Abstract

The main cause of morbidity and mortality in diabetes mellitus (DM) is cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here, we compared these two models for their effects on cardiac structure, function and transcriptome. Different doses of STZ and diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and nonobese sex- and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR and RNA-seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM affected left ventricular function and myocardial performance differently. T1DM displayed exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis, along with increased cardiac oxidative stress, CM DNA damage and senescence, when compared to T2DM in mice. T1DM and T2DM affected the whole cardiac transcriptome differently. In conclusion, the STZ-induced T1DM and T2DM mouse models showed significant differences in cardiac remodeling, function and the whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.

Keywords: type 1 diabetes mellitus; type 2 diabetes mellitus; cardiac cell senescence; streptozotocin; left ventricular remodeling; myocardial regeneration

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MDPI and ACS Style

Marino, F.; Salerno, N.; Scalise, M.; Salerno, L.; Torella, A.; Molinaro, C.; Chiefalo, A.; Filardo, A.; Siracusa, C.; Panuccio, G.; et al. Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy. Int. J. Mol. Sci. 2023, 24, 1132. https://doi.org/10.3390/ijms24021132

AMA Style

Marino F, Salerno N, Scalise M, Salerno L, Torella A, Molinaro C, Chiefalo A, Filardo A, Siracusa C, Panuccio G, et al. Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy. International Journal of Molecular Sciences. 2023; 24(2):1132. https://doi.org/10.3390/ijms24021132

Chicago/Turabian Style

Marino, Fabiola, Nadia Salerno, Mariangela Scalise, Luca Salerno, Annalaura Torella, Claudia Molinaro, Antonio Chiefalo, Andrea Filardo, Chiara Siracusa, Giuseppe Panuccio, and et al. 2023. "Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy" International Journal of Molecular Sciences 24, no. 2: 1132. https://doi.org/10.3390/ijms24021132

APA Style

Marino, F., Salerno, N., Scalise, M., Salerno, L., Torella, A., Molinaro, C., Chiefalo, A., Filardo, A., Siracusa, C., Panuccio, G., Ferravante, C., Giurato, G., Rizzo, F., Torella, M., Donniacuo, M., De Angelis, A., Viglietto, G., Urbanek, K., Weisz, A., ... Cianflone, E. (2023). Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy. International Journal of Molecular Sciences, 24(2), 1132. https://doi.org/10.3390/ijms24021132

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Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy

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