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Pharmacological basis of different targets for the treatment of atherosclerosis.

Abstract
The development of atherosclerotic plaque is a highly regulated and complex process which occurs as a result of structural and functional alterations in endothelial cells, smooth muscle cells (SMCs), monocytes/macrophages, T-lymphocytes and platelets. The plaque formation in the coronary arteries or rupture of the plaque in the peripheral vasculature in latter stages of atherosclerosis triggers the onset of acute ischemic events involving myocardium. Although lipid lowering with statins has been established as an important therapy for the treatment of atherosclerosis, partially beneficial effects of statins beyond decreasing lipid levels has shifted the focus to develop newer drugs that can affect directly the process of atherosclerosis. Blockade of renin angiotensin system, augmentation of nitric oxide availability, reduction of Ca(2+) influx, prevention of oxidative stress as well as attenuation of inflammation, platelet activation and SMC proliferation have been recognized as targets for drug treatment to control the development, progression and management of atherosclerosis. A major challenge for future drug development is to formulate a combination therapy affecting different targets to improve the treatment of atherosclerosis.
AuthorsHarjot K Saini, Yan-Jun Xu, Amarjit S Arneja, Paramjit S Tappia, Naranjan S Dhalla
JournalJournal of cellular and molecular medicine (J Cell Mol Med) 2005 Oct-Dec Vol. 9 Issue 4 Pg. 818-39 ISSN: 1582-1838 [Print] England
PMID16364193 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Nitric Oxide
  • Cholesterol
Topics
  • Animals
  • Atherosclerosis (drug therapy, pathology, physiopathology)
  • Cholesterol (metabolism)
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
  • Inflammation
  • Lipids (chemistry)
  • Nitric Oxide (metabolism)
  • Oxidative Stress
  • Platelet Activation (drug effects)
  • Renin-Angiotensin System (drug effects)

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