title: Top-down Proteomics: Technology Advancements and Applications to Heart Diseases.
abstract: Heart diseases are a leading cause of morbidity and mortality for both men and women worldwide, and impose significant economic burdens on the healthcare systems. Despite substantial effort over the last several decades, the molecular mechanisms underlying diseases of the heart remain poorly understood.
  
  
  
  Altered protein post-translational modifications (PTMs) and protein isoform switching are increasingly recognized as important disease mechanisms. Top-down high-resolution mass spectrometry (MS)-based proteomics has emerged as the most powerful method for the comprehensive analysis of PTMs and protein isoforms. Here, we will review recent technology developments in the field of top-down proteomics, as well as highlight recent studies utilizing top-down proteomics to decipher the cardiac proteome for the understanding of the molecular mechanisms underlying diseases of the heart. Expert commentary: Top-down proteomics is a premier method for the global and comprehensive study of protein isoforms and their PTMs, enabling the identification of novel protein isoforms and PTMs, characterization of sequence variations, and quantification of disease-associated alterations. Despite significant challenges, continuous development of top-down proteomics technology will greatly aid the dissection of the molecular mechanisms underlying diseases of the hearts for the identification of novel biomarkers and therapeutic targets.
authors.affiliation: a Department of Cell and Regenerative Biology , University of Wisconsin-Madison , Madison , WI , USA.|b Molecular and Cellular Pharmacology Training Program , University of Wisconsin-Madison , Madison , WI , USA.
authors.forename: Wenxuan
authors.initials: W
authors.lastname: Cai
authors.affiliation: c Department of Chemistry , University of Wisconsin-Madison , Madison , WI , USA.
authors.forename: Trisha M
authors.initials: TM
authors.lastname: Tucholski
authors.affiliation: a Department of Cell and Regenerative Biology , University of Wisconsin-Madison , Madison , WI , USA.|b Molecular and Cellular Pharmacology Training Program , University of Wisconsin-Madison , Madison , WI , USA.
authors.forename: Zachery R
authors.initials: ZR
authors.lastname: Gregorich
authors.affiliation: a Department of Cell and Regenerative Biology , University of Wisconsin-Madison , Madison , WI , USA.|c Department of Chemistry , University of Wisconsin-Madison , Madison , WI , USA.|d Human Proteomics Program , University of Wisconsin-Madison , Madison , WI , USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ge
mesh_terms: D015415:Biomarkers; D006331:Heart Diseases / Q000235:genetics* / Q000473:pathology; D006801:Humans; D013058:Mass Spectrometry; D020033:Protein Isoforms / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D020543:Proteome / Q000235:genetics*; D040901:Proteomics / Q000379:methods*
chemical_list: D015415:Biomarkers; D020033:Protein Isoforms; D020543:Proteome
keywords: Top-down mass spectrometry; heart diseases; myofilaments; post-translational modifications; quantitative analysis