Current knowledge into the role of the peptidylarginine deiminase (PAD) enzyme family in cardiovascular disease

Eur J Pharmacol. 2021 Jan 15:891:173765. doi: 10.1016/j.ejphar.2020.173765. Epub 2020 Nov 26.

Abstract

Peptidylarginine deiminase (PAD) family members have a vital role in maintaining the stability of the extracellular matrix (ECM) during remodelling in several heart diseases. PAD-mediated deamination, or citrullination, has been studied in different physiological and pathological conditions in the body. However, the role of PAD isoforms has not been fully studied in cardiovascular system. Citrullination is a post-translational modification that involves conversion of peptidyl-based arginine to peptidyl-based citrulline by PAD family members in a calcium-dependent manner. Upregulation of PADs have been observed in various cardiovascular diseases, including venous thrombosis, cardiac fibrosis, heart failure, atherosclerosis, coronary heart disease and acute inflammation. In this review, experimental aspects of in vivo and in vitro studies related to the roles PAD isoforms in cardiovascular diseases including mechanisms, pathophysiological and therapeutic properties are discussed. Pharmacological strategies for targeting PAD family proteins in cardiac diseases have not yet been studied. Furthermore, the role played by PAD family members in the remodelling process during the progression of cardiovascular diseases is not fully understood.

Keywords: Atherosclerosis; Cardiovascular diseases; Citrullination; Fibrosis; Heart failure; Myocardial infarction; PADs; Peptidylarginine deiminases; Thrombosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Atrial Remodeling
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / enzymology*
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular System / drug effects
  • Cardiovascular System / enzymology*
  • Cardiovascular System / physiopathology
  • Citrullination
  • Deamination
  • Enzyme Inhibitors / therapeutic use
  • Extracellular Matrix / enzymology*
  • Humans
  • Protein-Arginine Deiminases / antagonists & inhibitors
  • Protein-Arginine Deiminases / metabolism*
  • Vascular Remodeling
  • Ventricular Remodeling

Substances

  • Enzyme Inhibitors
  • Protein-Arginine Deiminases