Right ventricular cardiomyocyte expansion accompanies cardiac regeneration in newborn mice after large left ventricular infarcts
Tianyuan Hu, Mona Malek Mohammadi, Fabian Ebach, Michael Hesse, Michael I. Kotlikoff, Bernd K. Fleischmann
Tianyuan Hu, Mona Malek Mohammadi, Fabian Ebach, Michael Hesse, Michael I. Kotlikoff, Bernd K. Fleischmann
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Research Article Cardiology

Right ventricular cardiomyocyte expansion accompanies cardiac regeneration in newborn mice after large left ventricular infarcts

Abstract

Cauterization of the root of the left coronary artery (LCA) in the neonatal heart on postnatal day 1 (P1) resulted in large, reproducible lesions of the left ventricle (LV), and an attendant marked adaptive response in the right ventricle (RV). The response of both chambers to LV myocardial infarction involved enhanced cardiomyocyte (CM) division and binucleation, as well as LV revascularization, leading to restored heart function within 7 days post surgery (7 dps). By contrast, infarction of P3 mice resulted in cardiac scarring without a significant regenerative and adaptive response of the LV and the RV, leading to subsequent heart failure and death within 7 dps. The prominent RV myocyte expansion in P1 mice involved an acute increase in pulmonary arterial pressure and a unique gene regulatory response, leading to an increase in RV mass and preserved heart function. Thus, distinct adaptive mechanisms in the RV, such as CM proliferation and RV expansion, enable marked cardiac regeneration of the infarcted LV at P1 and full functional recovery.

Authors

Tianyuan Hu, Mona Malek Mohammadi, Fabian Ebach, Michael Hesse, Michael I. Kotlikoff, Bernd K. Fleischmann

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Figure 8

Different adaptive response of the RV of P1 MI and P3 MI hearts, and functional evidence of pulmonary arterial hypertension in P1 MI mice.

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Different adaptive response of the RV of P1 MI and P3 MI hearts, and fun...
(A and B) Images (A) and quantitation (B) of the wall thickness of heart sections stained for TNNI3 and costained with DAPI; dashed lines mark infarct area, double arrows indicate measuring sites. Scale bar: 1 mm. (C and D) RV heart sections stained for TNNI3 and costained with WGA and DAPI showing CM sizes (C) and quantification (D) of CM cross-sectional area in the RV. Scale bar: 20 μm. (E and F) RV heart sections costained for PECAM1, TNNI3, and with WGA and DAPI showing capillaries (E) and quantitation of capillary density (F). Scale bar: 20 μm. (G) Pulmonary artery acceleration time/pulmonary artery ejection time (PAAT/PAET) ratio obtained with Doppler measurements of flow velocity in the main pulmonary artery in P1 MI and sham mice. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 by 1-way ANOVA with Holm-Šidák post hoc test (B, D, and F) or unpaired, 2-tailed Student’s t test (G). NS, no significance.