SASAKI Daisuke    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Assistant Professor (Fixed Term)
Language	English
Title	Impact of Overexpression of GJA1 on Human iPS Cell-derived Cardiac Tissue with Disarray of Cardiomyocytes
Conference	第87回日本循環器学会学術集会
Conference Type	Nationwide Conferences
Presentation Type	Speech
Lecture Type	General
Publisher and common publisher	Takada Takuma, MATSUURA Katsuhisa, Iida Tatsuro, Koike Toshiharu, SASAKI Daisuke, YAMAGUCHI JUNICHI, SHIMIZU Tatsuya
Date	2023/03/10
Venue (city and name of the country)	福岡
Summary	Background: Non-failing heart is composed of several layers of aligned cardiomyocytes. Meanwhile, disarray of cardiomyocytes is commonly observed in failing heart. Previously, we succeeded in aligned and non-aligned human induced pluripotent stem cell-derived cardiac tissue with the micro-processed fibrin gel and demonstrated that non-aligned cardiac tissue (NACT) showed the deterioration of contractile force through dyssynchronous cardiomyocyte contraction compared with aligned cardiac tissue. Although there were no significant differences in the gene expression level of GJA1 between the two groups, the protein expression level of Cx43 was lower in NACT than aligned cardiac tissue. The aims of our study were to assess the effect of the overexpression of GJA1 on contractile force in NACT. Methods/Results: We used adeno-associated virus (AAV) to mediate the overexpression of GJA1 in NACT. The gene expression level of GJA1 in NACT with overexpression of GJA1 was approximately seven times higher than that in NACT with control AAV. Contrary to expectations, the spontaneous beating rate, contractile force at spontaneous beating rate, contractile force under the electrical stimulation of 75 ppm tended to decrease in NACT with overexpression of GJA1 compared with NACT with control AAV (43 ± 18 vs. 54 ± 2.4 bpm, p=0.20, 0.58 ± 0.37 vs. 0.88 ± 0.54 mN, p=0.29, and 0.52 ± 0.33 vs. 0.81 ± 0.51 mN, p=0.28, N=6, respectively). Conclusion: Cx43 might play a pivotal role for synchronous and strong contraction, but the overexpression of GJA1 did not contribute to increase the contractile force. The post-translational modification might be essential for improving the contractile force in failing heart with myocardial disarray.