Researchers at the University of Pennsylvania School of Medicine and Queen's University, Ontario, Canada report in the online edition of Nature Medicine this week that the COX enzymes – well-known for their contrasting role in cardiovascular biology – interact physically to form a previously unrecognized biochemical partnership and function in the development of blood vessels in a mouse model. 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 function independently from their mother.
"These observations prompt us to explore new roles for the COX enzymes in biology," says FitzGerald. "Perhaps their embrace will extend to other enzymes, such as the lipoxygenases and the nitric oxide synthases, in ways that prompt us to re-evaluate basic assumptions about the role of COX enzymes in physiology and disease."
"Perhaps this combination of COX enzymes will represent a new drug target," speculates Funk. "Blocking the COX dimer may alter the pattern of usefulness and/or safety that we associate with existing non-steroidal anti-inflammatory drugs." Funk, who has collaborated with FitzGerald at Penn over the last decade on this line of research, is now the Canada Research Chair of Physiology at Queen's University, Ontario.
Karen Kreeger | EurekAlert!
New way to look at cell membranes could change the way we study disease
19.11.2018 | University of Oxford
Controlling organ growth with light
19.11.2018 | European Molecular Biology Laboratory
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
19.11.2018 | Materials Sciences
19.11.2018 | Information Technology
19.11.2018 | Life Sciences