The Maastricht Acquisition Platform for Studying Mechanisms of Cell–Matrix Crosstalk (MAPEX): An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease
Abstract
:1. Introduction
2. Scientific Underpinning and Research Question
2.1. Loss of Mechanical Homeostasis
2.2. Pathophysiological Framework
2.2.1. Wall Shear Stress Homeostasis
2.2.2. Wall Stress Homeostasis
2.3. Focus of MAPEX Platform Infrastructure
- Preoperative 4D-flow MRI, to capture wall shear stress patterns in relation to local vessel geometry;
- Strain imaging during open-chest surgery, to capture local vessel wall deformations;
- Tissue sampling co-localised with local tissue strain and wall shear stress measurements;
- To capture tissue and cell-specific biomarkers, as well as ultrastructural properties;
- Inclusion of a large cohort (minimal target of 400) of aneurysm patients undergoing cardiac surgery, complemented by patients with normal aortic diameter as controls (with limited tissue sampling);
- Data structuring ready for (i) computational biomechanical modelling, (ii) omics, and (iii) artificial intelligence approaches, for data integration and interpretation, as well as new hypothesis generation.
3. Methodological Setup
3.1. Acquisition Platform Management
3.2. Study Population
3.3. Recruitment Procedure
3.4. Pre- and Peri-Operative Procedures
4. Materials and Data Processing
4.1. Location-Specific Characterisation Methods of Aortic Tissue
4.1.1. Aortic Tissue Samples
4.1.2. Histopathological Analysis
4.1.3. Genotyping and Omics-Approach
4.2. Circulating Markers and iPSC-Oriented Research
4.2.1. Circulating Blood Markers
4.2.2. Pluripotent Stem Cell Research
5. Statistics and Methodology
6. Research Scope
7. Clinical Application
8. Future Directions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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aTAA | HTAA | Controls | aTAAD | |
---|---|---|---|---|
Type of index event | Aneurysm | Heritable aneurysm | CABG/AVR | Type-A dissection |
Number of subjects | 86 | 9 | 30 | 20 |
Gender (male %) | 70 | 67 | 90 | 65 |
Age (years) | 60 ± 14 | 44 ± 14 | 63 ± 12 | 60 ± 14 |
BMI (kg/m3) | 26 ± 5 | 23 ± 4 | 26 ± 4 | 28 ± 7 |
Weight (kg) | 81 ± 17 | 67 ± 12 | 83 ± 16 | 85 ± 24 |
Aortic diameter (mm) | 53 [47;59] | 48 [40;60] | 41 [36;44] | 55 [52;52] |
Hypertension (%) | 73 | 33 | 77 | 95 |
Diabetes mellitus (%) | 5 | 11 | 7 | - |
Hypercholesterolemia (%) | 53 | - | 70 | 60 |
COPD (%) | 7 | 22 | 10 | 20 |
Myocardial infarction (%) | 9 | - | 23 | 20 |
Family history for CVD (%) | 20 | 56 | 53 | 20 |
Current smoker (%) | 9 | 22 | 27 | 25 |
Alcohol use (%) | 65 | 56 | 57 | 45 |
Aortic insufficiency (%) | 77 | 67 | 40 | 35 |
Aortic stenosis (%) | 20 | - | 60 | 5 |
Valve morphology (% BAV) | 31 | 44 | 27 | 10 |
LVEF (%) | 53 [46;59] | 55 [52;57] | 55 [45;60] | - |
Biomaterials | Storage | Analysis Material | Storage Temperature |
---|---|---|---|
Blood | EDTA BD Vacutainer | Plasma | <−80 °C |
PBMCs | <−80 °C | ||
Sodium Citrated BD Vacutainer | Serum | <−80 °C | |
Tissue | Serum free M199/DMEM medium | Tissue sections for smooth muscle cell isolation | 4 °C |
4% paraformaldehyde-fixed | Paraffin-embedded tissue sections | 20–22 °C | |
Fresh frozen in OCT | Fresh-frozen tissue sections | <−80 °C | |
RNA later | RNA stabilised tissue for gene expression | <−80 °C | |
Snap frozen in N2 | Snap-frozen tissue for gene expression | <−80 °C |
Category | Phenotypes | Marker of Target | Type of Analysis | Name of Stain/Assay | References |
---|---|---|---|---|---|
Tissue | Cell nuclei, extracellular matrix, cytoplasm, inflammatory infiltration, adipose tissue | VSMC nuclei | Histological | Haematoxylin and eosin | SOP 13LU-0406 |
Extracellular matrix | Collagen I and III | Histological | Picrosirius red (Direct red 80) | SOP 16CM-421 | |
Extracellular matrix | Elastin | Histological | Elastica van Gieson | SOP 12PL-0403 | |
Contractile VSMC | Calponin-1 (CNN1) | Immunohistological (IHC) | CNN1 stain | SOP 14LU-0412 | |
Contractile VSMC | Alpha-smooth muscle actin (α-SMA) | Immunohistological (IHC) | α-SMA stain | SOP 14LU-0404 | |
Vascular vitamin K status and vascular calcification | Uncarboxylated matrix gamma carboxyglutamate protein (ucMGP) | Immunohistological (IHC) | ucMGP stain | SOP 14LU-0413 | |
Proteinase inhibitor | Alpha-1 Antitrypsin (A1AT, SERPINA1) | Immunohistological (IHC) | SERPINA1 strain | SOP 22RK BG-439 | |
Blood serum | Breakdown products of elastin | Desmosine (DES) | Enzyme-linked immunosorbent assay (ELISA) | DES ELISA kit | n.a. |
Breakdown products of elastin | Isodesmosine (IDES) | Enzyme-linked immunosorbent assay (ELISA) | IDES ELISA kit | n.a. |
Gene | Transcript Reference (Ensembl) | Alternative Exon | Transcript Reference for Alternative Exon (Ensembl) |
---|---|---|---|
ABL1 | ENST00000372348 | ||
ACTA2 | ENST00000458208 | ||
ARIH1 | ENST00000379887 | ||
BGN | ENST00000331595 | ||
COL3A1 | ENST00000304636 | ||
EFEMP2/FBLN4 | ENST00000307998 | ||
ELN | ENST00000358929 | ||
EMILIN1 | ENST00000380320 | ||
FBN1 | ENST00000316623 | ||
FBN2 | ENST00000262464 | ||
FLNA | ENST00000369850 | ||
FOXE3 a | ENST00000335071 | ||
HCN4 | ENST00000261917 | ||
IPO8 | ENST00000256079 | ||
LMOD1 | ENST00000367288 | ||
LOX | ENST00000231004 | ||
LTBP3 | ENST00000301873 | ||
MAT2A | ENST00000306434 | ||
MFAP5 | ENST00000359478 | ||
MYH11 | ENST00000452625 | Exon 42B | ENST00000396324 |
MYLK | ENST00000360304 | ||
NOTCH1 | ENST00000277541 | ||
NPR3 | ENST00000265074 | ||
PLOD1 | ENST00000196061 | Exon 2A | ENST00000449038 |
PMEPA1/TMEPAI | ENST00000341744 | ||
PRKG1 b | ENST00000401604 | ||
ROBO4 | ENST00000306534 | ||
SKI | ENST00000378536 | ||
SLC2A10 | ENST00000359271 | ||
SMAD2 | ENST00000402690 | ||
SMAD3 | ENST00000327367 | Exon 1A | ENST00000439724 |
SMAD4 | ENST00000342988 | ||
SMAD6 | ENST00000288840 | ||
TGFB2 | ENST00000366929 | ||
TGFB3 | ENST00000238682 | ||
TGFBR | ENST00000374994 | ||
TGFBR2 | ENST00000359013 | ||
THSD4 | ENST00000261862 |
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Ganizada, B.H.; Reesink, K.D.; Parikh, S.; Ramaekers, M.J.F.G.; Akbulut, A.C.; Saraber, P.J.M.H.; Debeij, G.P.; MUMC-TAA Student Team; Jaminon, A.M.; Natour, E.; et al. The Maastricht Acquisition Platform for Studying Mechanisms of Cell–Matrix Crosstalk (MAPEX): An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease. Biomedicines 2023, 11, 2095. https://doi.org/10.3390/biomedicines11082095
Ganizada BH, Reesink KD, Parikh S, Ramaekers MJFG, Akbulut AC, Saraber PJMH, Debeij GP, MUMC-TAA Student Team, Jaminon AM, Natour E, et al. The Maastricht Acquisition Platform for Studying Mechanisms of Cell–Matrix Crosstalk (MAPEX): An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease. Biomedicines. 2023; 11(8):2095. https://doi.org/10.3390/biomedicines11082095
Chicago/Turabian StyleGanizada, Berta H., Koen D. Reesink, Shaiv Parikh, Mitch J. F. G. Ramaekers, Asim C. Akbulut, Pepijn J. M. H. Saraber, Gijs P. Debeij, MUMC-TAA Student Team, Armand M. Jaminon, Ehsan Natour, and et al. 2023. "The Maastricht Acquisition Platform for Studying Mechanisms of Cell–Matrix Crosstalk (MAPEX): An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease" Biomedicines 11, no. 8: 2095. https://doi.org/10.3390/biomedicines11082095