Therapeutic enzymes as non-conventional targets in cardiovascular impairments: A comprehensive review

Can J Physiol Pharmacol. 2022 Mar;100(3):197-209. doi: 10.1139/cjpp-2020-0732. Epub 2021 Dec 21.

Abstract

Over the last few decades, substantial progress has been made towards the understanding of cardiovascular diseases. In-depth mechanistic insights have also provided opportunities to explore novel therapeutic targets and to discover new treatment regimens. Therapeutic enzymes are examples of such opportunities. The enzymes protect against a variety of cardiovascular diseases, however, even minor malfunctioning of these enzymes may lead to deleterious outcomes. Owing to their great versatility, the inhibition and activation of these enzymes are key regulatory approaches to counter the onset and progression of several cardiovascular impairments. While cardiovascular remedies are already available in excess and are efficacious, a comprehensive description of novel therapeutic enzymes to combat cardiovascular diseases would still be of great benefit. In the light of this, the regulation of functional activities of these enzymes also opens a new avenue for the treatment approaches to be employed. This review describes the importance of non-conventional enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), phosphodiesterase (PDE), arginase, superoxide dismutase (SOD), thioredoxin reductase (TXNRD) and selenoprotein T (SELENOT), cytochrome b5 reductase 3 (CYB5R3), epoxide hydrolase (EHs), xanthine oxidoreductase (XOR), matrix metalloprotease (MMPs), and dopamine beta hydroxylase (DBH), as potential candidates in several cardiovascular disorders while highlighting some of the recently targeted therapeutic enzymes in cardiovascular diseases. We also discuss the role of intrinsic antioxidant defense system involved in cardioprotection followed by addressing some of the clinical investigations considering the use of antioxidant as a preferred therapy of cardiovascular complications.

Keywords: cardiovascular diseases; cardiovascular impairments; inhibiteurs; inhibitors; maladies cardiovasculaires; therapeutic enzymes; traitements enzymatiques; troubles cardiovasculaires.

Publication types

  • Review

MeSH terms

  • Antioxidants
  • Arginase
  • Cardiotonic Agents
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / enzymology*
  • Cardiovascular Diseases / etiology
  • Cytochrome-B(5) Reductase
  • Dopamine beta-Hydroxylase
  • Epoxide Hydrolases
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinases
  • Middle Aged
  • Molecular Targeted Therapy*
  • NADPH Oxidases
  • Phosphoric Diester Hydrolases
  • Selenoproteins
  • Superoxide Dismutase
  • Thioredoxin-Disulfide Reductase
  • Xanthine Dehydrogenase

Substances

  • Antioxidants
  • Cardiotonic Agents
  • SELENOT protein, human
  • Selenoproteins
  • Dopamine beta-Hydroxylase
  • Superoxide Dismutase
  • Xanthine Dehydrogenase
  • CYB5R3 protein, human
  • Cytochrome-B(5) Reductase
  • NADPH Oxidases
  • Thioredoxin-Disulfide Reductase
  • Phosphoric Diester Hydrolases
  • Epoxide Hydrolases
  • Matrix Metalloproteinases
  • Arginase