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New Role of COX Enzymes Discovered

Recent research has revealed that the COX enzymes interact physically in a biochemical partnership as well as function in the development of blood vessels. //

The study was conducted by researchers at the University of Pennsylvania School of Medicine and Queen's University, Ontario, Canada and reported in the online edition of Nature Medicine. The COX enzymes are well-known for their contrasting role in cardiovascular biology. Collaborators Garret FitzGerald, MD, Director of Penn's Institute for Translational Medicine and Therapeutics, and Colin Funk from Queen's University, say that the findings suggest new biological, developmental, and therapeutic roles for COX enzymes and prompt a re-evaluation of basic assumptions about the role of COX enzymes in disease.

COX-2 is the target of the now familiar COX inhibitors Vioxx and Celebrex. COX-1, the less celebrated sister, is the target of low-dose aspirin and older drugs, such as Advil and Naprosyn, which inhibit both COX-1 and COX-2 to prevent heart disease.

Researchers have known for some time that COX-1 and COX-2 pair up to function in the body. Even though they are interlocked, only one of them is active at a time in processing their substrate, arachidonic acid – from which prostaglandins, the fatty mediators of pain, inflammation, and heart attacks – are formed. The molecular structures of COX-1 and COX-2 are remarkably similar, but a subtle variation in their structure permits the construction of drugs that are selective in their inhibition for COX -2.

For this study the researchers developed a novel genetic mouse model that mimics the physiology of COX-2 inhibition. The investigators demonstrated that the COX-1:COX-2 partnership, or heterodimer, appears to play a critical role in the transformation that occurs in the blood vessels of newly born mice, shortly after birth, namely the closing of the ductus arterious. This necessary developmental step permits newborns to
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