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. Author manuscript; available in PMC: 2023 Apr 29.
Published in final edited form as: Circ Res. 2022 Apr 4;130(9):1345–1361. doi: 10.1161/CIRCRESAHA.121.320005

Figure 3. The ablation of cycling cardiomyocytes attenuated the beneficial effects of Harmine on LV systolic function after I/R MI.

Figure 3.

(A) Protocol using αDKRC (cardiomyocyte-specific αMHC-MerDreMer-Ki67p-RoxedCre)::RLTG (Rox-Lox-tdTomato-eGFP)/Rosa26-DTA (Diphtheria Toxin) (αDKRC::RLTG/DTA) and +::RLTG/DTA littermate controls treated with Tamoxifen (1 mg/kg IP [intraperitoneal] daily×5 d×2 cycles) followed by recovery period before undergoing 60 min of left anterior descending (LAD) artery-ligation ischemia and reperfusion (I/R myocardial infarction [MI]) and implantation of an osmotic minipump to deliver Harmine (10 mg/kg/day). Serial echocardiography was performed before and after MI. N=7 in the αDKRC::RLTG/DTA and N = 6 in the +::RLTG/DTA group. (B and C) The absolute values (%) (B) and percent changes (C) in left ventricular (LV) ejection fraction (EF) of αDKRC::RLTG/DTA and +::RLTG/DTA mice treated with harmine minipumps (10 mg/kg/day) after 60 minutes of I/R MI. Open and closed circles are means ± SDs of +::RLTG/DTA and αDKRC::RLTG/DTA mice, respectively. * denotes p = 1.0x10−4 and # p = 1.0x10−4 for the indicated time. p-values were calculated by student’s t-test. N=7 in the αDKRC::RLTG/DTA and N = 6 in the +::RLTG/DTA group. In panel C, p = 1.0x10−4 for the percent change in LVEF between +::RLTG/DTA and αDKRC::RLTG/DTA mice. p-values calculated by student’s t-test. (D and E) The absolute values (ul) (D) and percent changes (E) in LV end-systolic volume (ESV) of αDKRC::RLTG/DTA and +::RLTG/DTA mice treated with harmine minipumps (10 mg/kg/day) after 60 minutes of I/R MI. Open and closed circles are means ± SDs of +::RLTG/DTA and αDKRC::RLTG/DTA mice, respectively. * p = 4.0x10−3 for the indicated time. p-values were calculated by student’s t-test. N=7 in the αDKRC::RLTG/DTA and N = 6 in the +::RLTG/DTA group. In panel D, p = 8.0x10−2 for the percent change in LVEF between +::RLTG/DTA and αDKRC::RLTG/DTA mice. P-values calculated by student’s t-test. (F and G) The absolute values (%) (F) and percent changes (G) in LV end-diastolic volumes (EDV) of αDKRC::RLTG/DTA and +::RLTG/DTA mice treated with harmine minipumps (10 mg/kg/day) after 60 minutes of I/R MI. Open and closed circles are means ± SDs of +::RLTG/DTA and αDKRC::RLTG/DTA mice, respectively. N=7 in the αDKRC::RLTG/DTA and N = 6 in the +::RLTG/DTA group. In panel D, p = 5.6x10−1 for the percent change in LVEF between +::RLTG/DTA and αDKRC::RLTG/DTA mice. P-values calculated by student’s t-test.