Phosphoproteomic response of cardiac endothelial cells to ischemia and ultrasound

Uchenna Emechebe, David Giraud, Azzdine Ammi, Kristin L. Scott, Jon M. Jacobs, Jason E. McDermott, Igor V. Dykan, Nabil Alkayed, Anthony Barnes, Sanjiv Kaul, Catherine M. Davis

Research output: Contribution to journalArticlepeer-review

Abstract

Myocardial infarction and subsequent therapeutic interventions activate numerous intracellular cascades in every constituent cell type of the heart. Endothelial cells produce several protective compounds in response to therapeutic ultrasound, under both normoxic and ischemic conditions. How endothelial cells sense ultrasound and convert it to a beneficial biological response is not known. We adopted a global, unbiased phosphoproteomics approach aimed at understanding how endothelial cells respond to ultrasound. Here, we use primary cardiac endothelial cells to explore the cellular signaling events underlying the response to ischemia-like cellular injury and ultrasound exposure in vitro. Enriched phosphopeptides were analyzed with a high mass accuracy liquid chromatrography (LC) - tandem mass spectrometry (MS/MS) proteomic platform, yielding multiple alterations in both total protein levels and phosphorylation events in response to ischemic injury and ultrasound. Application of pathway algorithms reveals numerous protein networks recruited in response to ultrasound including those regulating RNA splicing, cell-cell interactions and cytoskeletal organization. Our dataset also permits the informatic prediction of potential kinases responsible for the modifications detected. Taken together, our findings begin to reveal the endothelial proteomic response to ultrasound and suggest potential targets for future studies of the protective effects of ultrasound in the ischemic heart.

Original languageEnglish (US)
Article number140683
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1869
Issue number9
DOIs
StatePublished - Sep 2021

Keywords

  • Endothelial cell
  • Heart
  • Ischemia
  • Phosphoproteomics
  • Proteomics
  • Ultrasound

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Phosphoproteomic response of cardiac endothelial cells to ischemia and ultrasound'. Together they form a unique fingerprint.

Cite this