title: Quantitative proteomics reveals differential regulation of protein expression in recipient myocardium after trilineage cardiovascular cell transplantation.
abstract: Intramyocardial transplantation of cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) derived from human induced pluripotent stem cells (hiPSCs) has beneficial effects on the post-infarction heart. However, the mechanisms underlying the functional improvements remain undefined. We employed large-scale label-free quantitative proteomics to identify proteins that were differentially regulated following cellular transplantation in a swine model of myocardial infarction (MI). We identified 22 proteins that were significantly up-regulated after trilineage cell transplantation compared to both MI and Sham groups. Among them, 12 proteins, including adenylyl cyclase-associated protein 1 and tropomodulin-1, are associated with positive regulation of muscular contraction whereas 11 proteins, such as desmoplakin and zyxin, are involved in embryonic and muscular development and regeneration. Moreover, we identified 21 proteins up-regulated and another 21 down-regulated in MI, but reversed after trilineage cell transplantation. Proteins up-regulated after MI but reversed by transplantation are related to fibrosis and apoptosis. Conversely, proteins down-regulated in MI but restored after cell therapy are regulators of protein nitrosylation. Our results show that the functionally beneficial effects of trilineage cell therapy are accompanied by differential regulation of protein expression in the recipient myocardium, which may contribute to the improved cardiac function.
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, USA.|Human Proteomics Program, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, USA.|Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Wenxuan
authors.initials: W
authors.lastname: Cai
authors.affiliation: Human Proteomics Program, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Yoonkyu
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Human Proteomics Program, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Huseyin
authors.initials: H
authors.lastname: Guner
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, USA.|Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, Madison, WI, USA.|Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Youngsook
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, USA.|Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, Madison, WI, USA.|Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI, USA.|Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kamp
authors.affiliation: Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA.|Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.|Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, USA.|Human Proteomics Program, University of Wisconsin-Madison, Madison, WI, USA.|Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, Madison, WI, USA.|Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI, USA.|Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ge
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D002853:Chromatography, Liquid / Q000379:methods; D019295:Computational Biology / Q000379:methods; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D033581:Stem Cell Transplantation / Q000379:methods*; D013552:Swine; D053719:Tandem Mass Spectrometry; D014183:Transplantation, Heterologous
keywords: Biomedicine; Cardiac regeneration; Heart disease; Label-free quantification; Large mammalian models; Stem cells