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