Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy
Abstract
:1. Introduction
2. Results
2.1. STZ-Based T1DM and T2DM Mouse Models Affected Global Left Ventricular Function Differently
2.2. STZ-Based T1DM and T2DM Mouse Models Affected Myocardial Performance Differently
2.3. STZ-Based T1DM and T2DM Mouse Models Affected Left Ventricular Remodeling Differently
2.4. STZ-Based T1DM and T2DM Mouse Models Affected Oxidative Stress and Cell Senescence Differently
2.5. The Global Transcriptome Profile Showed Different Gene-Expression Signatures in the STZ-Based T1DM and T2DM Mouse Models
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Mouse Cardiomyocyte Isolation
4.3. Echocardiography
4.4. Tissue Harvesting, Histology and Immunohistochemistry
4.5. Quantitative RT-PCR (qPCR)
4.6. RNA Sequencing
4.6.1. RNA Extraction
4.6.2. Library Preparation
4.6.3. Sequencing
4.7. RNA-Seq Data Analysis
4.8. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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CTRL (n = 10) | T1DM (n = 11) | T2DM (n = 12) | p-Value | |
---|---|---|---|---|
HR (bpm) | 446.67 ± 24.16 | 463.55 ± 49.13 | 442.25 ± 40.34 | 0.428 |
LVEDD (mm) | 4.06 ± 0.08 | 4.40 ± 0.20 | 3.95 ± 0.23 | <0.001 |
LVESD (mm) | 2.82 ± 0.07 | 3.41 ± 0.19 | 2.75 ± 0.30 | <0.001 |
EF (%) | 58.33 ± 2.32 | 45.63 ± 3.84 | 58.41 ± 6.55 | <0.001 |
FS (%) | 30.45 ± 1.63 | 22.60 ± 2.29 | 30.57 ± 4.49 | <0.001 |
GLS (%) | −21.49 ± 1.33 | −13.93 ± 3.38 | −18.49 ± 2.99 | <0.001 |
E (mm/sec) | 639.98 ± 88.09 | 702.06 ± 78.32 | 587.87 ± 73.18 | 0.008 |
A (mm/sec) | 399.20 ± 54.74 | 422.69 ± 57.17 | 411.68 ± 80.27 | 0.756 |
E/A | 1.62 ± 0.3 | 1.65 ± 0.19 | 1.47 ± 0.27 | 0.256 |
E′ (mm/sec) | −25.18 ± 3.10 | −21.68 ± 3.97 | −18.44 ± 4.96 | 0.005 |
E/E′ | 25.6 ± 3.5 | 33.10 ± 5.62 | 33.35 ± 7.24 | 0.009 |
E′/A′ | 1.15 ± 0.26 | 0.77 ± 0.11 | 0.97 ± 0.23 | 0.002 |
IVSd (mm) | 0.65 ± 0.06 | 0.62 ± 0.05 | 0.59 ± 0.04 | 0.067 |
LVPWd (mm) | 0.63 ± 0.07 | 0.64 ± 0.07 | 0.62 ± 0.05 | 0.628 |
Gene | Sequence (5′ -> 3′) |
---|---|
mGapdh | Fwd-CTCCACTCTTCCACCTTCG- |
Rev-GCCTCTCTTGCTCAGTGTCC- | |
mTgfb2 | Fwd-CCGCATCTCCTGCTAATGTTG- |
Rev-AATAGGCGGCATCCAAAGC- | |
mNppa | Fwd-CTGATGGATTTCAAGAACCTGCT- |
Rev-TCTCAGAGGTGGGTTGACCT- | |
mp21 | Fwd-AACATCTCAGGGCCGAAA- |
Rev-TGCGCTTGGAGTGATAGAAA- | |
mp16 | Fwd-GTGTGCATGACGTGCGGG- |
Rev-GCAGTTCGAATCTGCACCGTAG- | |
mp15 | Fwd-AGATCCCAACGCCCTGAAC- |
Rev-CCCATCATCATCACCTGGATT- | |
mp19 | Fwd-GCTCTGGCTTTCGTGAACATG- |
Rev-TCGAATCTGCACCGTAGTTGAG- | |
mMybpc2 | Fwd-CTGCTAGGGCCTGGTTAGAG- |
Rev-CCTTTTTGGCCGCTGGTTTA- | |
mIl-6 | Fwd-TGAGAAAAGAGTTGTGCAATGG- |
Rev-GGTACTCCAGAAGACCAGAGG- | |
mCcl11 | Fwd-TGCAGAGCTCCACAGCGCTT |
Rev-GGGTGAGCCAGCACCTGGGA | |
mPai-1 | Fwd-GGCCATTACTACGACATCCTG |
Rev-GGTCATGTTGCCTTTCCAGT | |
mIl1b | Fwd-TGCCACCTTTTGACAGTGATG |
Rev-TGATGTGCTGCTGCGAGATT | |
mGja1 | Fwd GGT GAT GAA CAG TCT GCC TTT CG |
Rev GTG AGC CAA GTA CAG GAG TGT G | |
mCol1a1 | Fwd CCT CAG GGT ATT GCT GGA CAA C |
Rev CAG AAG GAC CTT GTT TGC CAG G | |
mCol1a2 | Fwd TTC TGT GGG TCC TGC TGG GAA A |
Rev TTG TCA CCT CGG ATG CCT TGA G | |
mCol3a1 | Fwd GAC CAA AAG GTG ATG CTG GAC AG |
Rev CAA GAC CTC GTG CTC CAG TTA G | |
mMyl7 | Fwd AGG AAG CCA TCC TGA GTG CCT T |
Rev CAT GGG TGT CAG CGC AAA CAG T | |
mCasp3 | Fwd GGA GTC TGA CTG GAA AGC CGA A |
Rev CTT CTG GCA AGC CAT CTC CTC A | |
mBcl2 | Fwd CCT GTG GAT GAC TGA GTA CCT G |
Rev AGC CAG GAG AAA TCA AAC AGA GG | |
mBax | Fwd AGG ATG CGT CCA CCA AGA AGC T |
Rev TCC GTG TCC ACG TCA GCA ATC A | |
mFoxo3 | Fwd CCT ACT TCA AGG ATA AGG GCG AC |
Rev GCC TTC ATT CTG AAC GCG CAT G | |
mFoxo1 | Fwd CTA CGA GTG GAT GGT GAA GAG C |
Rev CCA GTT CCT TCA TTC TGC ACT CG | |
mIL1a | Fwd AGGGAGTCAACTCATTGGCG |
Rev TGGCAGAACTGTAGTCTTCGT | |
mTp53 | Fwd ATGGCCATCTACAAGAAGTCACAG |
Rev ATCGGAGCAGCGCTCATG | |
mMyh7 | Fwd GCTGGAAGATGAGTGCTCAGAG |
Rev TCCAAACCAGCCATCTCCTCTG | |
mRyr2 | Fwd ACCTACTCCGAAGGCTGGTGTT |
Rev TTCTTCCGAGGCAGCACCAAAG | |
mAtp2a | Fwd GTGAAGTGCCATCAGTATGACGG |
Rev GTGAGAGCAGTCTCGGTAGCTT | |
mPnl | Fwd GGACCAAAGGAACTTGCCAGCT |
Rev CAACAGGCAGCCAAATGTGAGC |
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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
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 StyleMarino, 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 StyleMarino, 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