Ablation of Vitamin D Signaling in Cardiomyocytes Leads to Functional Impairment and Stimulation of Pro-Inflammatory and Pro-Fibrotic Gene Regulatory Networks in a Left Ventricular Hypertrophy Model in Mice
Abstract
:1. Introduction
2. Results
2.1. Generation and Characterization of Cardiomyocyte-Specific VDR Knockout Mice
2.2. Development of Afterload-Induced Cardiac Hypertrophy Is Not Modulated by Loss of VDR in Cardiomyocytes
2.3. Lack of VDR Signaling in Cardiomyocytes Aggravates TAC-Induced LV Functional Impairment
2.4. Spatial Transcriptomics Reveal More Pronounced Pro-Inflammatory and Pro-Fibrotic Gene Regulatory Networks in Hypertrophic Cardiac Tissue Niches of TAC VDRCM-KO Mice
3. Discussion
4. Material and Methods
4.1. Animals
4.2. Transverse Aortic Constriction (TAC)
4.3. Doppler Echocardiography
4.4. Central Arterial and Cardiac Pressure Measurements
4.5. Biochemical Analysis
4.6. Tissue Harvesting and Histological Analysis
4.7. RNA Isolation and Quantitative Real-Time PCR
4.8. Statistical Analysis of Phenotyping Data
4.9. Spatial Transcriptomics and Bioinformatic Analysis
4.9.1. Spatial Transcriptomics Data Preprocessing
4.9.2. Data Integration
4.9.3. Differential Expression and Marker Identification
4.9.4. Functional Enrichment Analysis
4.9.5. Differential Gene Regulatory Network Analysis
4.9.6. Co-Expression Modules and Gene-Regulatory Networks (GRN)
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Zupcic, A.; Latic, N.; Oubounyt, M.; Ramesova, A.; Carmeliet, G.; Baumbach, J.; Elkjaer, M.L.; Erben, R.G. Ablation of Vitamin D Signaling in Cardiomyocytes Leads to Functional Impairment and Stimulation of Pro-Inflammatory and Pro-Fibrotic Gene Regulatory Networks in a Left Ventricular Hypertrophy Model in Mice. Int. J. Mol. Sci. 2024, 25, 5929. https://doi.org/10.3390/ijms25115929
Zupcic A, Latic N, Oubounyt M, Ramesova A, Carmeliet G, Baumbach J, Elkjaer ML, Erben RG. Ablation of Vitamin D Signaling in Cardiomyocytes Leads to Functional Impairment and Stimulation of Pro-Inflammatory and Pro-Fibrotic Gene Regulatory Networks in a Left Ventricular Hypertrophy Model in Mice. International Journal of Molecular Sciences. 2024; 25(11):5929. https://doi.org/10.3390/ijms25115929
Chicago/Turabian StyleZupcic, Ana, Nejla Latic, Mhaned Oubounyt, Alice Ramesova, Geert Carmeliet, Jan Baumbach, Maria L. Elkjaer, and Reinhold G. Erben. 2024. "Ablation of Vitamin D Signaling in Cardiomyocytes Leads to Functional Impairment and Stimulation of Pro-Inflammatory and Pro-Fibrotic Gene Regulatory Networks in a Left Ventricular Hypertrophy Model in Mice" International Journal of Molecular Sciences 25, no. 11: 5929. https://doi.org/10.3390/ijms25115929