Growth and Remodelling in the Porcine Heart-- Pushing Mathematics through Experiments
Lead Research Organisation:
CARDIFF UNIVERSITY
Department Name: Sch of Engineering
Abstract
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Publications
Ahmad F
(2023)
Quantifying the microstructural and biomechanical changes in the porcine ventricles during growth and remodelling.
in Acta biomaterialia
| Description | This study has so far generated baseline data, describing the biomechanical and microstructural changes in the left and right ventricular myocardial tissue during growth and remodelling. The results so far reveal that ventricular tissue exhibits non-linear, anisotropic, and viscoelastic behaviour during biomechanical testing. An increase in the stiffness is noted for the left and right ventricular free wall from neonatal to adulthood, and viscoelasticity. Microstructural analyses reveals a consistent pattern of change in cardiomyocyte rotation and dispersion in the left and right ventricle. In contrast, collagen fibrils rotation and dispersion continuously increased between neonatal to adulthood in both ventricles. |
| Exploitation Route | These data should prove valuable to researchers in developing age-specific, constitutive models for more accurate computational simulations. |
| Sectors | Healthcare |
| Description | Cardiff University/CSC - iCDT (Xu) |
| Amount | £70,000 (GBP) |
| Organisation | Chinese Scholarship Council |
| Sector | Charity/Non Profit |
| Country | China |
| Start | 10/2021 |
| End | 09/2024 |
| Description | Cardiff University/CSC International Centre for Doctoral Training |
| Amount | £70,000 (GBP) |
| Organisation | Chinese Scholarship Council |
| Sector | Charity/Non Profit |
| Country | China |
| Start | 10/2021 |
| End | 09/2024 |
| Title | Biomechanical data |
| Description | Data describing the biaxial behaviour of cardiac tissue harvested from porcine across 4 age groups. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | No |
| Impact | This work is currently under review for publication. |
| Title | Gene expression analysis of immature, juvenile and adult porcine hearts |
| Description | Background: This study was performed in order to compare in porcine the known changes in gene expression corresponding to phenotypic switches in the structure and function of the cardiac muscle. A variety of important and functionally relevant markers were chosen to be evaluated using immature (new born), juvenile (7 month) and adult (42 month) porcine cardiac tissue. Tissue was taken from individual atrial and ventricular chambers of samples so that chamber specific information of gene expression could also be gathered. The initial gene expression panel was; Titin: N2B: stiff isoform (functional marker) Titin: N2BA : compliant isoform (functional marker Titin: N2B-N2BA all isoforms (functional marker) PCNA: Proliferating cell nuclear antigen (proliferation marker) TNNI1: slow skeletal Troponin I1 (functional marker) TNNI3: cardiac Troponin I3 (functional marker) TNNT1: slow skeletal Troponin T1 (functional marker) TNNT2: cardiac Troponin T2 (functional marker) Methods: Cardiac tissues were isolated from freshly slaughtered tissues and stored in stabilisation solution. Biopsies were then frozen in liquid nitrogen and pulverised in a frozen steel chamber in the presence of Trizol. RNA was isolated from the extracts using the RNA Easy Plus kit. cDNA was synthesised using 2 micrograms of RNA. RT-QPCR analysis was performed by absolute quantitation of gene expression levels using plasmid cloned PCR products to produce a standard curve. Actin gene expression was used to normalise expression levels. In the boxplots of data the y axis denotes the gene of interest divided by actin gene expression levels. Results: TNNI1: This marker was highly expressed in the atria of juvenile (7M) cardiac tissue but at low levels in all other chambers of 7M and 42M (adult) animals. Individual left and right chambers of 7M animals showed equivalent expression. TNNI3: TNNI3 expression was significantly higher in adult ventricles ~ 5-fold higher. TNNT1: TNNT1 expression was higher in the ventricles of adult (42M) cardiac tissue. Chamber specific analysis shows expression levels are higher yet in the left ventricular compared to the right in aged hearts. TNNT2: A pronounced increase in the left side of the heart of TNNT2 was noted in younger animals but this was less evident in adult animal hearts. Expression was highest in the ventricles of adult tissue. N2BA: Overall expression is higher in adult ventricles and reflects context dependent expression levels rather than protein content. Analysis of newborn cardiac tissue would help shed light on this. N2B: This isoform of Titin appears to be predominantly expressed in juvenile and adult heart muscle, with a pronounced increase evident in adult ventricles. N2B-N2BA: When the expression levels all Titin isoforms are analysed using primers targeting an early exon (exons 49-50) the highest expression is seen in adult ventricles and is higher in the right compared to the left ventricle. PCNA: Juvenile and adult tissues all showed relatively low expression levels of PCNA indicating minimal cellular proliferation within heart muscle tissues, although comparison with immature tissues is required to confirm this assumption. |
| Type Of Material | Data analysis technique |
| Year Produced | 2022 |
| Provided To Others? | No |
| Impact | Conclusion: Thus far, steady state quantitiative gene expression analysis is able to distinguish juvenile and adult cardiac muscle and even distinguish specific chambers using different gene primer sets. This data confirms that the 7 month old hearts are indeed still in the process of development. There is one dataset that is missing, that is for immature (new born) tissue. It is anticipated these latter samples will be acquired presently and the compete gene expression profiles can be made available to the team. We also have access to metabolic gene markers and further sets of structural markers which will be also used to determine expression levels when the full sample set is available. |
| Title | TPEF/SHG data describing structure of cardiac tissue during G & R |
| Description | The three-dimensional microstructure was investigated via two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) microscopy on optically cleared tissues, describing the 3D orientation, rotation and dispersion of the cardiomyocytes and collagen fibrils. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | No |
| Impact | This data is incorporated into a journal paper, which is currently under review. |
| Description | Irvin Teh (Leeds University) |
| Organisation | University of Leeds |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Motivated to understand the alignment of fibres within the cardiac tissue, to corroborate our biomechanical data. |
| Collaborator Contribution | Expertise in post-processing DT-MRI datasets, to derive metrics that describe fibre alignment and orientation. |
| Impact | This collaboration incorporates image processing (computer science) and biomechanics (engineering). |
| Start Year | 2022 |
| Description | TBRC (Bristol University) |
| Organisation | University of Bristol |
| Department | Translational Biomedical Research Centre (TBRC) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Motivated to understand the orientation of cardiac fibres and how these differ with growth and remodelling. |
| Collaborator Contribution | Providing an environment for acquiring tissue from the same species, controlled for physiological factors including state of cardiac arrest. |
| Impact | This is a multi-disciplinary collaboration between the Translation Biomedical Research Centre (School of Medicine, Bristol) and Biomechanics (School of Engineering, Cardiff) |
| Start Year | 2022 |