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Immunology‚ Endocrine & Metabolic Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Immunology‚ Endocrine and Metabolic Agents)

Volume 12 Issue 4
ISSN: 1871-5222
eISSN: 1875-5844


   All Titles

  The Role of the Endothelium in the Pathogenesis of Atherosclerosis and its Therapeutic Implications
  pp.279-288 (10) Authors: Marc J. George, Rajesh Kharbanda, Raymond J. MacAllister

Atherosclerosis is the major cause of morbidity and mortality worldwide. Endothelial dysfunction is central to the pathogenesis of atherosclerosis, initiating a triad of lipid accumulation in the vessel wall, a co-existent inflammatory response and proliferation of smooth muscle cells. It has also been implicated in the precipitation of acute ischaemia, and the determination of the extent of injury following such complications.

Healthy endothelium regulates numerous blood vessel functions, including vascular tone, cell adhesiveness, and coagulation through the production of mediators. The best characterised of these are the vasodilators, nitric oxide (NO), prostacyclin, and endothelium derived hyperpolarising factor, and the vasoconstrictors thromboxane and endothelin. The endothelium itself may also be maintained by bone-marrow derived endothelial progenitor cells (EPC) which are mobilised in response to vascular injury and have angiogenic and proliferative properties.

Understanding of the biology of the endothelium in atherosclerosis has led to new treatments and more may follow. Work is ongoing into NO bioavailability, prostacyclin agonists, endothelin and thromboxane antagonists, novel antiinflammatory and anti-oxidative agents as well as means of harnessing the properties of EPCs. It is hoped that this research will yield clinically useful approaches that will retard the progression of atherosclerosis and reduce the incidence or consequences of acute complications.

  Keywords: Atherosclerosis, endothelin, endothelium, endothelial dysfunction, inflammation, myocardial ischaemia, myocardial infarction, nitric oxide, novel therapies, progenitor cells, prostacyclin, thromboxane
  Affiliation: Clinical Pharmacology and Therapeutics, University College London Hospital. Correspondence to Rayne Institute, 5 University Street, London, WC1 6JF, UK.
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