Emerging role of oxidative stress in metabolic syndrome and cardiovascular diseases: important role of Rac/NADPH oxidase

J Pathol. 2013 Nov;231(3):290-300. doi: 10.1002/path.4255.


'Oxidative stress' is a term defining states of elevated reactive oxygen species (ROS) levels. Normally, ROS control several physiological processes, such as host defence, biosynthesis of hormones, fertilization and cellular signalling. However, oxidative stress has been involved in different pathologies, including metabolic syndrome and numerous cardiovascular diseases. A major source of ROS involved in both metabolic syndrome and cardiovascular pathophysiology is the NADPH oxidase (NOX) family of enzymes. NOX is a multi-component enzyme complex that consists of membrane-bound cytochrome b-558, which is a heterodimer of gp91phox and p22phox, cytosolic regulatory subunits p47phox and p67phox, and the small GTP-binding protein Rac1. Rac1 plays many important biological functions in cells, but perhaps the most unique function of Rac1 is its ability to bind and activate the NOX complex. Furthermore, Rac1 has been reported to be a key regulator of oxidative stress through its co-regulatory effects on both nitric oxide (NO) synthase and NOX. Therefore, the main goal of this review is to give a brief outline about the important role of the Rac1-NOX axis in the pathophysiology of both metabolic syndrome and cardiovascular disease.

Keywords: cardiovascular disease; metabolic syndrome; oxidative stress.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / therapeutic use
  • Cardiovascular Agents / therapeutic use
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / enzymology*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / enzymology*
  • NADPH Oxidases / antagonists & inhibitors
  • NADPH Oxidases / metabolism*
  • Oxidative Stress* / drug effects
  • Signal Transduction
  • rac GTP-Binding Proteins / antagonists & inhibitors
  • rac GTP-Binding Proteins / metabolism*
  • rac1 GTP-Binding Protein / metabolism


  • Antioxidants
  • Cardiovascular Agents
  • Enzyme Inhibitors
  • NADPH Oxidases
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein