Impact of High-Dose Irradiation on Human iPSC-Derived Cardiomyocytes Using Multi-Electrode Arrays: Implications for the Antiarrhythmic Effects of Cardiac Radioablation.
Jae Sik KimSeong Woo ChoiYun-Gwi ParkSung Joon KimChang Heon ChoiMyung-Jin ChaJi Hyun ChangPublished in: International journal of molecular sciences (2021)
Cardiac radioablation is emerging as an alternative option for refractory ventricular arrhythmias. However, the immediate acute effect of high-dose irradiation on human cardiomyocytes remains poorly known. We measured the electrical activities of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) upon irradiation with 0, 20, 25, 30, 40, and 50 Gy using a multi-electrode array, and cardiomyocyte function gene levels were evaluated. iPSC-CMs showed to recover their electrophysiological activities (total active electrode, spike amplitude and slope, and corrected field potential duration) within 3-6 h from the acute effects of high-dose irradiation. The beat rate immediately increased until 3 h after irradiation, but it steadily decreased afterward. Conduction velocity slowed in cells irradiated with ≥25 Gy until 6-12 h and recovered within 24 h; notably, 20 and 25 Gy-treated groups showed subsequent continuous increase. At day 7 post-irradiation, except for cTnT , cardiomyocyte function gene levels increased with increasing irradiation dose, but uniquely peaked at 25-30 Gy. Altogether, high-dose irradiation immediately and reversibly modifies the electrical conduction of cardiomyocytes. Thus, compensatory mechanisms at the cellular level may be activated after the high-dose irradiation acute effects, thereby, contributing to the immediate antiarrhythmic outcome of cardiac radioablation for refractory ventricular arrhythmias.
Keyphrases
- genome wide
- high dose
- dna methylation
- copy number
- endothelial cells
- high glucose
- stem cell transplantation
- induced pluripotent stem cells
- low dose
- left ventricular
- radiation induced
- drug induced
- heart failure
- gene expression
- hepatitis b virus
- respiratory failure
- radiation therapy
- blood pressure
- intensive care unit
- carbon nanotubes
- induced apoptosis
- aortic dissection
- cell proliferation
- high throughput
- endoplasmic reticulum stress
- acute respiratory distress syndrome
- cell cycle arrest
- genome wide identification
- newly diagnosed