Engineered Aging Cardiac Tissue Chip Model for Studying Cardiovascular Disease.

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Aging Biology

Background:

• Global aging population drives demand for better cardiovascular disease models.
• Existing models often fail to capture the complexities of aging hearts and infarction.
• Need for platforms that integrate hemodynamic stress and aging phenotypes.

Purpose of the Study:

• To develop a cardiac tissue chip model simulating an infarcted aging heart.
• To investigate cellular senescence and its role in cardiac pathology.
• To establish a platform for drug screening in age-related cardiovascular diseases.

Main Methods:

• Induced cellular senescence in H9c2 myoblasts using low-dose doxorubicin.
• Engineered cardiac tissue fibers from senescent cells and applied hemodynamic loading.
• Modeled myocardial ischemia using hypoxic treatment.
• Analyzed morphological and molecular markers of senescence and cardiac function.

Main Results:

• Doxorubicin induced senescence with characteristic morphological and molecular changes (e.g., enlarged nuclei, p16INK4a, p53, ROS expression).
• Engineered tissues under load maintained cell alignment and cardiac characteristics.
• The model successfully recapitulated myocardial infarction hallmarks, including increased cell death and elevated ANP/BNP expression.

Conclusions:

• A novel cardiac tissue chip model effectively mimics key aspects of the infarcted aging heart.
• The methodology allows for the generation of stress-induced aging cardiac cell phenotypes.
• This platform offers a valuable tool for studying age-related cardiovascular disease and for drug development.