Quantitative temporal analysis of protein dynamics in cardiac remodeling

J Mol Cell Cardiol. 2018 Aug;121:163-172. doi: 10.1016/j.yjmcc.2018.07.126. Epub 2018 Jul 19.

Abstract

Cardiac remodeling (CR) is a complex dynamic process common to many heart diseases. CR is characterized as a temporal progression of global adaptive and maladaptive perturbations. The complex nature of this process clouds a comprehensive understanding of CR, but greater insight into the processes and mechanisms has potential to identify new therapeutic targets. To provide a deeper understanding of this important cardiac process, we applied a new proteomic technique, PALM (Pulse Azidohomoalanine in Mammals), to quantitate the newly-synthesized protein (NSP) changes during the progression of isoproterenol (ISO)-induced CR in the mouse left ventricle. This analysis revealed a complex combination of adaptive and maladaptive alterations at acute and prolonged time points including the identification of proteins not previously associated with CR. We also combined the PALM dataset with our published protein turnover rate dataset to identify putative biochemical mechanisms underlying CR. The novel integration of analyzing NSPs together with their protein turnover rates demonstrated that alterations in specific biological pathways (e.g., inflammation and oxidative stress) are produced by differential regulation of protein synthesis and degradation.

Keywords: Azidohomoalanine; Cardiac remodeling; Isoproterenol; Metabolic labeling; Proteomics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Heart / growth & development
  • Heart / physiopathology*
  • Heart Failure / chemically induced
  • Heart Failure / genetics*
  • Heart Failure / physiopathology
  • Humans
  • Isoproterenol / toxicity
  • Mice
  • Myocardium / metabolism
  • Protein Biosynthesis / genetics
  • Proteome / genetics*
  • Ventricular Remodeling / genetics*

Substances

  • Proteome
  • Isoproterenol