Adult and neonatal models of chemogenetic heart failure caused by oxidative stress
Fotios Spyropoulos, Apabrita Ayan Das, Markus Waldeck-Weiermair, Shambhu Yadav, Arvind K. Pandey, Ruby Guo, Taylor A. Covington, Venkata Thulabandu, Kosmas Kosmas, Benjamin Steinhorn, Mark A. Perrella, Xiaoli Liu, Helen Christou, Thomas Michel
Fotios Spyropoulos, Apabrita Ayan Das, Markus Waldeck-Weiermair, Shambhu Yadav, Arvind K. Pandey, Ruby Guo, Taylor A. Covington, Venkata Thulabandu, Kosmas Kosmas, Benjamin Steinhorn, Mark A. Perrella, Xiaoli Liu, Helen Christou, Thomas Michel
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Research Letter Cardiology

Adult and neonatal models of chemogenetic heart failure caused by oxidative stress

Abstract

Authors

Fotios Spyropoulos, Apabrita Ayan Das, Markus Waldeck-Weiermair, Shambhu Yadav, Arvind K. Pandey, Ruby Guo, Taylor A. Covington, Venkata Thulabandu, Kosmas Kosmas, Benjamin Steinhorn, Mark A. Perrella, Xiaoli Liu, Helen Christou, Thomas Michel

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Figure 1

A chemogenetic/transgenic model of neonatal heart failure.

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A chemogenetic/transgenic model of neonatal heart failure. (A) Breeding ...
(A) Breeding strategy for heterozygous DAAO-TGCar pups treated in utero. Created with BioRender.com. E, embryonic day; PN, postnatal day. (B) M-mode images of the left ventricle and (C) echocardiographic parameters of ejection fraction (EF), fractional shortening (FS), end-systolic (ESV) and end-diastolic (EDV) volume, and anterior (AWTd) and posterior (PWTd) wall thickness in neonates exposed to d-alanine (0.4 M) (red squares) or l-alanine (0.4 M) (blue circles) from E8.5 to PN0. (D) Baseline HyPer ratio and (E) HyPer and tetramethylrhodamine methyl ester perchlorate (TMRM) images of cardiomyocytes from neonates (PN0) exposed to d-alanine or l-alanine. Quantification of (F) HyPer ratio, (G) mitoSOX, and (H) TMRM fluorescence in arbitrary units (a.U.). (I) Correlation between TMRM and HyPer (r = 0.857, P = 0.0004); dashed lines represent 95% CI. (J) Quantification of TUNEL staining (apoptosis) and Ki67 (proliferation). *P < 0.05, ***P < 0.001, ****P < 0.0001 by unpaired t test. Values shown as mean ± SEM. (K) Volcano plot showing protein abundances in d- versus l-alanine–exposed neonatal hearts; fold-changes and P values are log-transformed. Differentially expressed proteins (P = 0.05; FDR = 0.1) displayed as upregulated (red) and downregulated (blue). Proteins not significantly changed indicated in gray.