@article{53bc587e4ba24fb499cbc2a1d888574d,
title = "Integrated proteomics reveals alterations in sarcomere composition and developmental processes during postnatal swine heart development",
abstract = "The neonatal swine heart possesses an endogenous ability to regenerate injured myocardium through the proliferation of pre-existing cardiomyocyte (CM) populations. However, this regenerative capacity is lost shortly after birth. Normal postnatal developmental processes and the regenerative capacity of mammalian hearts are tightly linked, but not much is known about how the swine cardiac proteome changes throughout postnatal development. Herein, we integrated robust and quantitative targeted “top-down” and global “bottom-up” proteomic workflows to comprehensively define the dynamic landscape of the swine cardiac proteome throughout postnatal maturation. Using targeted top-down proteomics, we were able to identify significant alterations in sarcomere composition, providing new insight into the proteoform landscape of sarcomeres that can disassemble, a process necessary for productive CM proliferation. Furthermore, we quantified global changes in protein abundance using bottom-up proteomics, identified over 700 differentially expressed proteins throughout postnatal development, and mapped these proteins to changes in developmental and metabolic processes. We envision these results will help guide future investigations to comprehensively understand endogenous cardiac regeneration toward the development of novel therapeutic strategies for heart failure.",
keywords = "Global proteomics, Heart development, Maturation, Swine, Targeted proteomics",
author = "Aballo, {Timothy J.} and Roberts, {David S.} and Bayne, {Elizabeth F.} and Wuqiang Zhu and Gregory Walcott and Mahmoud, {Ahmed I.} and Jianyi Zhang and Ying Ge",
note = "Funding Information: Financial support was provided by the National Institutes of Health (NIH) R01 HL096971 (to Y.G.), HL156855 (to W.Z. and Y.G.). Y.G. would also like to acknowledge R01 GM117058, GM125085, HL109810 and S10 OD018475. J.Z. would like to acknowledge R01 HL131017 and R01 HL149137. T.JA. would like to acknowledge support from the Training Program in Molecular and Cellular Pharmacology, T32 GM008688. D.S.R. acknowledges the support from the American Heart Association Predoctoral Fellowship Grant No. 832615/David S. Roberts/2021. E.F·B. would like to acknowledge support from NIH R01HL148059. We thank Morgan W. Mann for helping with the bottom-up proteomic analysis scripting. Some aspects of the TOC and Fig. 1A were created using http://BioRender.com. Funding Information: Financial support was provided by the National Institutes of Health (NIH) R01 HL096971 (to Y.G.), HL156855 (to W.Z. and Y.G.). Y.G. would also like to acknowledge R01 GM117058, GM125085, HL109810 and S10 OD018475. J.Z. would like to acknowledge R01 HL131017 and R01 HL149137. T.JA. would like to acknowledge support from the Training Program in Molecular and Cellular Pharmacology, T32 GM008688. D.S.R. acknowledges the support from the American Heart Association Predoctoral Fellowship Grant No. 832615/David S. Roberts/2021. E.F·B. would like to acknowledge support from NIH R01HL148059 . We thank Morgan W. Mann for helping with the bottom-up proteomic analysis scripting. Some aspects of the TOC and Fig. 1 A were created using http://BioRender.com . Publisher Copyright: {\textcopyright} 2023 Elsevier Ltd",
year = "2023",
month = mar,
doi = "10.1016/j.yjmcc.2023.01.004",
language = "English (US)",
volume = "176",
pages = "33--40",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
}