High resolution mapping of the cardiac transmural proteome using reverse phase protein microarrays

Troy Anderson, Julia Wulfkuhle, Emanuel Petricoin, Raimond L. Winslow

Research output: Contribution to journalArticlepeer-review

Abstract

The expression level of proteins governing the electrical excitability of and conduction within ventricular myocardium are known to vary as a function of distance through the heart wall. The expression patterns of a subset of these proteins are altered in disease. Precise measurement of such patterns is therefore essential to understanding structure-function relationships within the heart in health and disease. Here, we report a new experimental approach using reverse-phase protein microarrays to map the left ventricular transmural proteome. This approach can yield submillimeter spatial resolution, and when coupled with the method of array microenvironment normalization, reduces nonbiological components of variability to ∼10% of overall study variability. In addition, the experimental design provides sufficient statistical power to detect small, yet potentially biologically significant expression changes on the order of 1.1-fold. The usefulness of this technique is demonstrated by mapping the transmural expression of Serca2a in the left ventricle of 12 canine hearts, each in one of three states: normal, dyssynchronous heart failure, and dyssynchronous heart failure followed by cardiac resynchronization therapy. We confirm the existence of a 40% transmural gradient (epi>endo) of Serca2a, and demonstrate the ability of this technique to yield highly significant transmural expression differences within each individual heart.

Original languageEnglish (US)
JournalMolecular and Cellular Proteomics
Volume10
Issue number7
DOIs
StatePublished - Jul 2011

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Fingerprint

Dive into the research topics of 'High resolution mapping of the cardiac transmural proteome using reverse phase protein microarrays'. Together they form a unique fingerprint.

Cite this