[John Vane, 1927-2004, the pharmacologist of the vascular endothelium [corrected]].
The work of John Vane greatly contributed to the use of aspirin in cardiology. The impact of aspirin administration at low dose for the prevention of stroke or coronary attack results from its effect on enzymes regulating the production of prostaglandins. After understanding the mechanism of interaction between aspirin and the vascular endothelium, Vane proposed assigning a major physiological function to the vascular endothelium which then became a pharmacological target for new drugs. Using an ingenious "real time" biological assay of bloodstream hormones irrigating an isolated organ called the "blood-bathed organ cascade", John Vane developed a system for highly sensitive monitoring of several mediators like angiotensin, bradykinin and prostaglandins and discovered prostacyclin, a potent platelet aggregation inhibitor. Vane explained anti-inflammatory drugs effects (among which aspirin remains the leader) through their activity on cyclo-oxygenase and inhibition of prostacyclin and thromboxane production. Another cyclooxygenase isoform, so-called type 2, has been discovered in 1991. Thus, besides the constitutive COX-1, participating to stomach protection and renal artery vasodilatation, a COX-2 enzyme is existing, induced by inflammatory phenomenons and cytokines stimulation, allowing to design specific inhibitors "coxibs", playing an increasing but controversial role in the struggle against inflammation. He won Albert Lasker Prize in 1977 and Nobel Prize in medicine and physiology (shared with Sune Bergström and Bengt I. Samuelson) in 1982.
Chast
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Service de Pharmacologie-Toxicologie de l'Hôtel-Dieu, 1, Place du Parvis Notre-Dame, F 75181 Paris Cedex 04, France. francois.chast@htd.ap-hop-paris.fr
D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D005602:France; D049673:History, 20th Century; D006801:Humans; D010827:Physiology / Q000266:history*