Introduction: Myocardial fibrosis and dysfunction is one of the major cardiac complications of long-term diabetes. Prolonged hyperglycemia is known to induce myocardial dysfunction often leading up to heart failure. Hypothesis: The objective of this study was to investigate the cardioprotective effect of glycyrrhizin (GLC) on myocardial damage in engineered in-vitro human cardiac tissues. Engineered 3D tissue chips present an ideal microenvironment via therapeutically relevant interfaces to study molecular- and cellular-level events and mimic human-specific disease states, and identify new therapeutic targets in vitro. Methods: AC16 human cardiomyocyte cells were used to 3D bioprint cardiac tissue chips based on prior publishedmore »
A 3D Bioprinted Human Cardiac Cell Platform to Model the Pathophysiology of Diabetes
Type-II diabetes (T2D) patients affected by underlying hyperglycemic (high glucose/blood sugar) conditions often suffer from cardiac atrophy, resulting in tissue mass reduction and debilitating cardiac health. To understand pathophysiological mechanisms during progression of cardiac atrophy, a 3D bioprinted organoid platform was developed from a mixture of hydrogels containing human cardiac cells, including cardiomyocytes (CM), fibroblasts (CF) and endothelial cells (EC), to mimic the functionality of the in-vivo tissue. The organoids were cultured using normoglycemic- or hyperglycemic-conditions. The expression of essential biomarkers in these organoids, for myocardin (Myocd), troponin-I (TRP-I), fibroblast protein-1 (FSP-1) and endothelin-1 (ET-1) was confirmed. To assess the physiological cellular connections during hyperglycemia, the presence of Connexin-43 (CX-43) was assessed in the presence of a CX-43 blocker, gap26. Epigenomic tools were used to simultaneously interrogate histone-modifications by histone 3 lysine 9 mono-methylation (H3K9me1) along with the co-regulation of inflammatory mediators, such as the high mobility group box 1 (HMGB1) and toll like receptor 4 (TLR4) in the cardiac organoids cultured using normal versus hyperglycemic conditions. Organoids exposed to high glucose showed an increased expression of H3K9me1 as well as inflammatory mediators HMGB1 and TLR4. Hyperglycemia also exhibited alterations in expression of Myocd and FSP-1 in the organoids, compared more »
- Award ID(s):
- 1927628
- Publication Date:
- NSF-PAR ID:
- 10276585
- Journal Name:
- Circulation research
- Volume:
- 127
- Issue:
- S-1
- Page Range or eLocation-ID:
- A465-A465
- ISSN:
- 2683-8567
- Sponsoring Org:
- National Science Foundation
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