Role of protein deimination in cardiovascular diseases: potential new avenues for diagnostic and prognostic biomarkers

Expert Rev Proteomics. 2021 Dec;18(12):1059-1071. doi: 10.1080/14789450.2021.2018303. Epub 2022 Jan 12.

Abstract

Introduction: Arginine deimination (citrullination) is a post-translational modification catalyzed by a family of peptidyl arginine deiminase (PAD) enzymes. Cell-based functional studies and animal models have manifested the key role of PADs in various cardiovascular diseases (CVDs).

Area covered: This review summarizes the past 10 years of knowledge on the role of PADs in CVD pathogenesis. It focuses on the PAD functions and diverse citrullinated proteins in cardiovascular conditions like deep vein thrombosis, ischemia/reperfusion, and atherosclerosis. Identification of PAD isoforms and citrullinated targets are essential for directing diagnosis and clinical intervention. Finally, anti-citrullinated protein antibodies (ACPAs) are addressed as an independent risk factor for cardiovascular events.

Expert opinion: PAD is an unique family of enzymes that permanently converts amino acid arginine to amino acid citrulline in protein . Overexpression or increased activity of PAD has been observed in various CVDs with acute and chronic inflammation as the background. Importantly, far beyond being simply involved in forming neutrophil extracellular traps (NETs), accumulating evidence indicated PAD activation as a trigger for numerous processes, such as transcriptional regulation, endothelial dysfunction, and thrombus formation. In summary, the findings so far have testified the important role of deimination in cardiovascular biology, while more basic and translational studies are essential for further exploration.

Keywords: NF-κB; Peptidylarginine deiminase; atherosclerosis; cardiovascular; citrullination; endothelial dysfunction; fibrosis; inflammation; neutrophil extracellular traps; thrombosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cardiovascular Diseases*
  • Citrullination*
  • Prognosis
  • Protein Processing, Post-Translational
  • Protein-Arginine Deiminases / genetics
  • Protein-Arginine Deiminases / metabolism

Substances

  • Biomarkers
  • Protein-Arginine Deiminases