Cyclooxygenases and the cardiovascular system

Pharmacol Ther. 2021 Jan;217:107624. doi: 10.1016/j.pharmthera.2020.107624. Epub 2020 Jul 5.


Cyclooxygenase (COX)-1 and COX-2 are centrally important enzymes within the cardiovascular system with a range of diverse, sometimes opposing, functions. Through the production of thromboxane, COX in platelets is a pro-thrombotic enzyme. By contrast, through the production of prostacyclin, COX in endothelial cells is antithrombotic and in the kidney regulates renal function and blood pressure. Drug inhibition of COX within the cardiovascular system is important for both therapeutic intervention with low dose aspirin and for the manifestation of side effects caused by nonsteroidal anti-inflammatory drugs. This review focuses on the role that COX enzymes and drugs that act on COX pathways have within the cardiovascular system and provides an in-depth resource covering COX biology and pharmacology. The review goes on to consider the role of COX in both discrete cardiovascular locations and in associated organs that contribute to cardiovascular health. We discuss the importance of, and strategies to manipulate the thromboxane: prostacyclin balance. Finally within this review the authors discuss testable COX-2-hypotheses intended to stimulate debate and facilitate future research and therapeutic opportunities within the field.

Keywords: Aspirin; Celecoxib; Cyclooxygenase; Fish oil; Heart attack; Ibuprofen.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Aspirin / pharmacology
  • Brain / drug effects
  • Brain / metabolism
  • Cardiovascular Physiological Phenomena
  • Cardiovascular System / drug effects*
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / pharmacology*
  • Drug Stability
  • Endothelial Cells / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Kidney / drug effects
  • Kidney / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Prostaglandins / metabolism
  • Temperature
  • Thromboxanes / metabolism
  • Thymus Gland / drug effects
  • Thymus Gland / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Prostaglandins
  • Thromboxanes
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin