Proteome Profiling of Brain Vessels in a Mouse Model of Cerebrovascular Pathology
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Mice
2.2. Surgical Extraction of Cerebral Arteries
2.3. Cerebrovascular Proteomics Workflow
2.4. Generation of Statistically Significant Protein Lists
2.5. Characterization and Classification of Proteins
2.6. Comparison against Public Transcriptomics Datasets
2.7. Comparison against the Public Human Extracellular Vesicles (EV) Database
2.8. Proteomics of Plasma and Plasma EVs
2.9. Formatting Guideline Used for Genes and Proteins
3. Results
3.1. Characterization of Proteins Detected in Mouse Brain Vessels
3.2. Proteins with Altered Levels in the Brain Vessels of TGF and WT Mice
3.3. Comparison against Published Transcriptomics in Mouse Brain Vascular Cells
3.4. Translatability of Findings to Human
3.5. Blood Biomarker Potential in Human
4. Discussion
4.1. Perturbation in Vascular Tone and Vasomotricity
4.1.1. Increased Vascular Tone
4.1.2. Attempt to Compensate by Promoting Vasodilation
4.2. Cerebrovascular Remodeling
4.2.1. Vascular Remodeling via Promotion of Cell Proliferation
4.2.2. Attempt to Attenuate Vascular Remodeling
4.3. Chronic Inflammation
4.3.1. Proteins Indicative of an Inflammatory Process
4.3.2. Attempt at Reducing Inflammation
4.3.3. Blood Biomarker and Translatability to Humans
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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ID (Human) | Common Name | Vesiclepedia Identified Molecule | Reported Detected in Vascular Cell and/or Blood, to Date | Type | |||||
---|---|---|---|---|---|---|---|---|---|
Vascular [Ref. ID] | Blood [Ref. ID] | Primary HBEC | HBEC EV | Plasma (Depleted) | Plasma EV | ||||
p | r | ||||||||
ACTA2 | Actin Alpha 2 | X | X | Endothelial [48,49] | Plasma [50,51] | X | X | X | X |
ANKRD24 | Ankyrin Repeat Domain 24 | X | - | - | |||||
DLL3 | Delta-Like Canonical Notch Ligand 3 | X | X | - | - | X | |||
ADGRG2 (GPR64) | Adhesion G Protein-Coupled Receptor G2 (also known as G Protein-Coupled Receptor 64) | X | X | - | - | ||||
IGDCC3 | Immunoglobulin Superfamily, DCC Subclass, Member 3 | X | - | - | X | ||||
KALRN | Kalirin RhoGEF Kinase | X | X | - | Plasma [52] | X | |||
NUBPL | Nucleotide Binding Protein-Like | X | X | - | - | ||||
PTPRN2 | Protein Tyrosine Phosphatase, Receptor Type N2 | X | - | - | |||||
TANC1 | Tetratricopeptide Repeat, Ankyrin Repeat, and Coiled-Coil Containing 1 | X | X | - | - | X | X | X | |
ZFYVE26 | Zinc Finger FYVE-Type Containing 26 | X | X | - | - | X | |||
DDX11 | DEAD/H-Box Helicase 11 | X | X | - | - | X | |||
DNAJA3 | DnaJ Heat Shock Protein Family (Hsp40) Member A3 | X | X | - | - | ||||
KRT24 | Keratin 24 | X | X | - | Plasma [50] | X | X | ||
NLRP5 | NOD-like Receptor Family Pyrin Domain Containing 5 | - | - | X | |||||
POF1B | POF1B Actin Binding Protein | X | - | - | |||||
PTPRD | Protein Tyrosine Phosphatase Receptor Type D | X | - | - | X | X | |||
RNGTT | RNA Guanylyltransferase And 5′-Phosphatase | X | X | - | - | ||||
RP1L1 | Retinitis Pigmentosa 1-like 1 | - | - | X | |||||
TACSTD2 | Tumor Associated Calcium Signal Transducer 2 | X | Endothelial [53] | - | |||||
ZFYVE27 | Zinc Finger FYVE-Type Containing 27 | X | X | - | - |
Protein | KEGG | Reactome | PANTHER | Common |
---|---|---|---|---|
ACTA2 | Vascular smooth muscle contraction | Muscle contraction | Alzheimer disease—presinilin | ✓✓✓ |
Motor proteins | Signal transduction | Signaling | ||
Apelin signaling pathway | - | Inflammation | ||
Relaxin signaling pathway | - | Cytoskeletal regulation by Rho GPTase | ||
ANKRD24 | - | - | - | |
DLL3 | Endocrine resistance | Developmental biology | Angiogenesis | ✓✓✓ |
Notch signaling pathway | - | Notch signaling pathway | ||
Th1 Th2 cell differenciation | - | - | ||
Pathways in cancer | - | - | ||
ADGRG2 | - | - | - | |
IGDCC3 | - | - | - | |
KALRN | - | Developmental biology | - | ✓ |
- | Signal transduction | - | ||
NUBPL | - | Metabolism | - | ✓ |
PTPRN2 | Type 1 diabetes mellitus | Immune system | - | ✓✓ |
TANC1 | - | - | - | |
ZFYVE26 | - | - | - | |
DDX11 | Cell cycle | Cellular responses to stimuli | - | ✓ |
DNAJA3 | Viral carcinogenesis | - | - | ✓ |
KRT24 | Estrogen signaling pathway | Developmental biology | - | ✓✓ |
Staphylococcus aureus infection | - | - | ||
NLRP5 | - | - | - | |
POF1B | - | - | - | |
PTPRD | Cell adhesion molecules | Neuronal system | - | ✓✓ |
RNGTT | mRNA surveillance pathway | Gene expression | - | ✓✓ |
- | Metabolism of RNA | - | ||
- | Disease | - | ||
RP1L1 | - | - | - | |
TACSTD2 | - | - | - | |
ZFYVE27 | Endocytosis | - | - | ✓ |
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Haqqani, A.S.; Mianoor, Z.; Star, A.T.; Detcheverry, F.E.; Delaney, C.E.; Stanimirovic, D.B.; Hamel, E.; Badhwar, A. Proteome Profiling of Brain Vessels in a Mouse Model of Cerebrovascular Pathology. Biology 2023, 12, 1500. https://doi.org/10.3390/biology12121500
Haqqani AS, Mianoor Z, Star AT, Detcheverry FE, Delaney CE, Stanimirovic DB, Hamel E, Badhwar A. Proteome Profiling of Brain Vessels in a Mouse Model of Cerebrovascular Pathology. Biology. 2023; 12(12):1500. https://doi.org/10.3390/biology12121500
Chicago/Turabian StyleHaqqani, Arsalan S., Zainab Mianoor, Alexandra T. Star, Flavie E. Detcheverry, Christie E. Delaney, Danica B. Stanimirovic, Edith Hamel, and AmanPreet Badhwar. 2023. "Proteome Profiling of Brain Vessels in a Mouse Model of Cerebrovascular Pathology" Biology 12, no. 12: 1500. https://doi.org/10.3390/biology12121500