A myocardial infarct border-zone-on-a-chip demonstrates distinct regulation of cardiac tissue function by an oxygen gradient.
Publication Year:
2022
PubMed ID:
36475790
Funding Grants:
Public Summary:
This study developed a “border-zone-on-a-chip” model that mimics the oxygen gradient found between healthy and damaged heart tissue after a myocardial infarction (heart attack). Using this microengineered system, researchers exposed lab-grown cardiac tissue to controlled oxygen levels and observed how varying oxygen conditions affected heart cell behavior and function. They found that tissues in an oxygen gradient—similar to the real post-infarct border zone—showed slower calcium signaling, weaker contraction strength, and increased activation of inflammatory pathways, all key features of heart injury. These effects were distinct from those seen in tissues exposed to uniform oxygen conditions, whether normal or low. Overall, the model provides a powerful new way to study how oxygen gradients regulate cardiac function and gene expression, offering insights into heart repair and disease mechanisms after injury.
Scientific Abstract:
After a myocardial infarction, the boundary between the injured, hypoxic tissue and the adjacent viable, normoxic tissue, known as the border zone, is characterized by an oxygen gradient. Yet, the impact of an oxygen gradient on cardiac tissue function is poorly understood, largely due to limitations of existing experimental models. Here, we engineered a microphysiological system to controllably expose engineered cardiac tissue to an oxygen gradient that mimics the border zone and measured the effects of the gradient on electromechanical function and the transcriptome. The gradient delayed calcium release, reuptake, and propagation; decreased diastolic and peak systolic stress; and increased expression of inflammatory cascades that are hallmarks of myocardial infarction. These changes were distinct from those observed in tissues exposed to uniform normoxia or hypoxia, demonstrating distinct regulation of cardiac tissue phenotypes by an oxygen gradient. Our border-zone-on-a-chip model advances functional and mechanistic insight into oxygen-dependent cardiac tissue pathophysiology.