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miR-146a Suppresses SUMO1 Expression and Induces Cardiac Dysfunction in Maladaptive Hypertrophy

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posted on 2019-08-03, 00:33 authored by Jae Gyun OhJae Gyun Oh, Shin Watanabe, Ahyoung Lee, Przemek A. Gorski, Philyoung Lee, Dongtak Jeong, Lifan Liang, Yaxuan Liang, Alessia Baccarini, Susmita Sahoo, Brian D Brown, Roger J. Hajjar, Changwon Kho

Table I. Calcium transient and contractility parameters of cardiomyocytes infected with Ad_pre-mir-146a or Ad_decoy-146a.

Top table, isolated mouse cardiomyocytes were infected with Ad_pre-mir-146a (MOI=50) for 24h. Data represent the mean ± s.e.m. in all panels (n=100-150 cells/4 hearts).

Bottom table, isolated mouse cardiomyocytes were infected with Ad_decoy-146a (MOI=50) for 24h. Data represent the mean ± s.e.m. in all panels (n=100-150 cells/4 hearts).

Table II. Echocardiographic parameters of mice injected with rAAV9_pre-mir-146a.

Data represent the mean ± s.e.m. of cardiac functional parameters 4 weeks post-injection.

Table III. Hemodynamic parameters of mice injected with rAAV9_pre-mir-146a.

Data represent the mean ± s.e.m. of cardiac functional parameters 4 weeks post-injection. Max dPdt, maximum dP/dt; Min dPdt, minimum dP/dt.

Table IV. Echocardiographic parameters of mice injected with rAAV9_decoy-146a.

Data represent the mean ± s.e.m. of cardiac functional parameters 4 weeks post-injection.

Table V. Hemodynamic parameters of mice injected with rAAV9_decoy-146a.

Data represent the mean ± s.e.m. of cardiac functional parameters 4 weeks post-injection.

Table VI. Echocardiographic parameters of SUMO1 TG mice injected with rAAV9_pre-mir-146a.

Data represent the mean ± s.e.m. of cardiac functional parameters 8 weeks post-injection. NL, Negative littermate; SUMO1 TG, Cardiac-specific Cre/loxP-conditional Sumo1-transgenic mice

Table VII. Cardiac cellular composition.

Isolated cardiac cells were sorted with FACS and analyzed. Data represent the mean ± s.e.m. (n=5).

Funding

SOURCES OF FUNDING This work is supported by NIH R00 HL116645 (C. K.). RJH is funded by NIH R01 HL117505, HL 119046, HL129814, 128072, HL131404, R01HL135093, a P50 HL112324, and a Transatlantic Fondation Leducq grant. We would like to acknowledge the Gene Therapy Resource Program (GTRP) of the National Heart, Lung, and Blood Institute, National Institutes of Health for providing the gene vectors used in this study. J.G.O was funded by AHA 17POST33410877.

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