The Role of Pathological Mechanical Environment on Cardiomyocyte Function in Hypoplastic Left Heart Syndrome.
- Left heart hypoplastic syndrome (HLHS) is a congenital heart defect (CHD) consisting of malformations in the left heart causing significantly inhibited blood flow. Currently surgical procedures have allowed infants to survive this condition into adulthood; however, these surgeries do not restore normal structure or function to the heart. Although improved treatment is desired, lack of understanding ... read moreto the cause of HLHS hinders development. Therefore, this study aimed to isolate the role of the real-time stretched mechanical environment on healthy and diseased cardiac cell development. The mechanical environments were generated by a custom-built cell stretching device and tests were performed to validate output. To study HLHS, a nitrofen-induced disease rat model was created and fetal hearts were isolated at various time points. These hearts were characterized by qRT-PCR and Western blotting to determine phenotypic traits of the disease model. Cardiac cells from these fetal hearts were then cultured while stretched by our device and analyzed by the same methods. Based on our analysis, we determined relatively good correlation between the designated parameters and the actual output of the device in terms of membrane stretch and frequency; however improvements could be made. Additionally, CHD fetal hearts were determined to have shifts in gene expression and protein content related to decrease in contractile function and maturity. Furthermore, culture of cells under mechanical stimulation demonstrated increased gene expression conveying improved functionality and maturation. However, current incompatibility of myocyte adhesion to the silicone culture membrane under mechanical stretch limited our analysis for specific effects of different types of mechanical stimulation. Based on these results, application of mechanical cues characteristic of normal myocardial stretch to healthy or diseased cardiomyocytes could be utilized to promote gene expression for improved myocyte function.read less
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