Role of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors, angiotensin-converting enzyme inhibitors, cyclooxygenase-2 inhibitors, and aspirin in anti-inflammatory and immunomodulatory treatment of cardiovascular diseases

Am J Cardiol. 2003 Jun 19;91(12A):12H-18H. doi: 10.1016/s0002-9149(03)00429-6.


The immunologic response in atherosclerosis involves not only intrinsic cells of the artery wall, but also circulating leukocytes, lymphocytes, and macrophages. Interaction of various arms of the immune response modulates plaque development and stability, and it is conceivable that immunologic effects of some cardiovascular therapies may contribute to their mechanism of benefit. The preponderance of data has accrued with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Statin effects, such as inhibition of T cell activation, tissue factor expression, or reduction of platelet hyperreactivity, may elicit beneficial effects in vitro and in vivo in patients with coronary artery disease. Moreover, aspirin may limit oxidation of lipoproteins and fibrinogen, and it may inhibit cytokine-induced nitric oxide synthase II expression. The hypothesis that selective inhibition of cyclooxygenase-2 (COX-2) may increase risk of myocardial infarction is controversial and may also be of questionable clinical significance. Finally, angiotensin-converting enzyme (ACE) inhibitors not only reduce proinflammatory mediators, such as interleukin-6, but also enhance the concentration of anti-inflammatory cytokines, such as interleukin-10. Because ACE is expressed at the shoulder region of atherosclerotic plaques, and ACE activity is enhanced in unstable plaques, ACE inhibition may also contribute to plaque stability. This article reviews the potential immunomodulatory potencies of aspirin, COX-2 inhibitors, statins, and ACE inhibitors as established pharmacotherapy in patients with coronary artery disease.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / immunology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / immunology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Aspirin / immunology
  • Aspirin / therapeutic use*
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / immunology
  • Cyclooxygenase 2
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / immunology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Inflammation / drug therapy
  • Isoenzymes / antagonists & inhibitors*
  • Membrane Proteins
  • Prostaglandin-Endoperoxide Synthases
  • Renin-Angiotensin System / immunology


  • Adjuvants, Immunologic
  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Inflammatory Agents, Non-Steroidal
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin