Effect of uric acid on inflammatory COX-2 and ROS pathways in vascular smooth muscle cells

J Recept Signal Transduct Res. 2017 Oct;37(5):500-505. doi: 10.1080/10799893.2017.1360350. Epub 2017 Aug 3.


Hyperuricemia is thought to play a role in cardiovascular diseases (CVD), including hypertension, coronary artery disease and atherosclerosis. However, exactly how uric acid contributes to these pathologies is unknown. An underlying mechanism of inflammatory diseases, such as atherosclerosis, includes enhanced production of cyclooxygenase-2 (COX-2) and superoxide anion. Here, we aimed to examine the effect of uric acid on inflammatory COX-2 and superoxide anion production and to determine the role of losartan. Primarily cultured vascular smooth muscle cells (VSMCs) were time and dose-dependently induced by uric acid and COX-2 and superoxide anion levels were measured. COX-2 levels were determined by ELISA, and superoxide anion was measured by the superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome c method. Uric acid elevated COX-2 levels in a time-dependent manner. Angiotensin-II receptor blocker, losartan, diminished uric-acid-induced COX-2 elevation. Uric acid also increased superoxide anion level in VSMCs. Uric acid plays an important role in CVD pathogenesis by inducing inflammatory COX-2 and ROS pathways. This is the first study demonstrating losartan's ability to reduce uric-acid-induced COX-2 elevation.

Keywords: COX-2; Uric acid; VSMC; inflammation; losartan; superoxide.

MeSH terms

  • Angiotensin II / metabolism
  • Animals
  • Cyclooxygenase 2 / genetics*
  • Disease Models, Animal
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Hypertension / pathology
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Losartan / administration & dosage
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Proto-Oncogene Proteins / genetics*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Signal Transduction / drug effects
  • Superoxides / antagonists & inhibitors
  • Uric Acid / administration & dosage


  • Proto-Oncogene Proteins
  • Reactive Oxygen Species
  • Superoxides
  • Angiotensin II
  • Uric Acid
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Receptor Protein-Tyrosine Kinases
  • Ros1 protein, rat
  • Losartan