KATP channel-dependent metaboproteome decoded: Systems approaches to heart failure prediction, diagnosis, and therapy

D. Kent Arrell, Jelena Zlatkovic Lindor, Satsuki Yamada, Andre Terzic

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Systems biology provides an integrative platform by which to account for the biological complexity related to cardiac health and disease. In this way, consequences of ATP-sensitive K+ (KATP) channel deficiency for heart failure prediction, diagnosis, and therapy were resolved recently at a proteomic level. Under stress-free conditions, knockout of the Kir6.2 K ATP channel pore induced metabolic proteome remodelling, revealing overrepresentation of markers of cardiovascular disease. Imposed stress precipitated structural and functional defects in Kir6.2-knockout hearts, decreasing survival and validating prediction of disease susceptibility. In the setting of hypertension, a leading risk for heart failure development, proteomic analysis diagnosed the metabolism-centric impact of KATP channel deficiency in disease. Bioinformatic interrogation of KATP channel-dependent proteome prioritized heart-specific adverse effects, exposing cardiomyopathic traits of aggravated contractility, fibrosis, and ventricular hypertrophy. In dilated cardiomyopathy induced by Kir6.2-knockout pressure overload, proteomic remodelling was exacerbated, underlying a multifaceted molecular pathology that indicates the necessity for a broad-based strategy to achieve repair. Embryonic stem cell intervention in cardiomyopathic K ATP channel knockout hearts elicited a distinct proteome signature that forecast amelioration of adverse cardiac outcomes. Functional/structural measurements validated improved contractile performance, reduced ventricular size, and decreased cardiac damage in the treated cohort, while systems assessment unmasked cardiovascular development as a prioritized biological function in stem cell-reconstructed hearts. Thus, proteomic deconvolution of KATP channel-deficient hearts provides definitive evidence for the channels homeostatic contribution to the cardiac metaboproteome and establishes the utility of systems-oriented approaches to predict disease susceptibility, diagnose consequences of heart failure progression, and monitor therapy outcome.

Original languageEnglish (US)
Pages (from-to)258-266
Number of pages9
JournalCardiovascular research
Issue number2
StatePublished - May 1 2011


  • ATP-sensitive K channel
  • Bioinformatics
  • Cardiac
  • Genetics
  • Heart disease
  • K channel
  • Kir6.2
  • Metabolism
  • Networks
  • Protein expression
  • Proteomics
  • Regenerative medicine
  • SUR2A
  • Stem cells
  • Systems biology

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'KATP channel-dependent metaboproteome decoded: Systems approaches to heart failure prediction, diagnosis, and therapy'. Together they form a unique fingerprint.

Cite this