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Niacin, or vitamin B3, is the one approved drug that elevates"good" cholesterol (high density lipoprotein, HDL) while depressing "bad" cholesterol(low density lipoprotein , LDL), and has thereby attracted muchattention from patients and physicians. Niacin keeps fat frombreaking down, and so obstructs the availability of LDL buildingblocks. Patients often stop taking niacin because it causes uncomfortablefacial flushing, an effect caused by the release of a fat calledprostaglandin or (PG)D2. PGD2 is the primary cause of the unwantedvasodilation, the "niacin flush." The dilation occurs when bloodvessels widen from relaxed smooth muscle cells within vessel walls. PGD2, formed by an enzyme called COX-2 and released by immune andskin cells, acts on a muscle cell-surface receptor called DP1 tocause the flushing. In fact, a combination of a DP1- blocking drugand niacin is being evaluated in a large clinical trial todetermine its effectiveness in reducing heart attacks , as opposed to other drugs that reduce LDL cholesterol. In work published in the Journal of Clinical Investigation this month, first authors Wenliang Song, MD, research assistantprofessor, and Jane Stubbe, PhD, postdoctoral fellow, in thePerelman School of Medicine, University of Pennsylvania, and theircolleagues now question the wisdom of blocking DP1 in patientsprone to cardiovascular disease, especially those taking niacin. Drawing evidence from studies in mice and humans, they show thatplatelets -- complicated cells circulating in the bloodstream thatstick together in the first phase of blood clotting -- make PGD2,which acts as a brake via DP1 on their own activation. This issurprising as PGD2 is made in platelets by COX-1, the targetinhibited by low-dose aspirin. COX-1 in platelets also makes thromboxane (Tx)A2, another fat thatactivates platelets. As low-dose aspirin is cardioprotective bythinning blood, the benefit from shutting down platelet TxA2 trumpsthe potential risk of suppressing platelet PGD2 production. To gather more information on the potential risks from blockingDP1, the Penn investigators used mice lacking the DP1 receptor.However, unlike humans, mice do not express DP1 in their platelets."Frankly, because of this, we did not expect to detect any signalof cardiovascular hazard in the mice," notes senior author GarretFitzGerald, MD, director of the Institute for TranslationalMedicine and Therapeutics. However, deletion of DP1 made mice somewhat more susceptible tohardening of the arteries, the formation of aneurysm , thrombosis, and in some cases, high blood pressure. The researchers suggest that these findings are reflective of DP1expression in vascular and immune cells in mice, just as in humans,despite its absence on mouse platelet cells. Turning back to humans, the Penn investigators discovered thatniacin evoked COX-1- dependent formation of both TxA2 and PGD2 inplatelets and that a DP1 blockade enhanced the effect of TxA2 onplatelet activation. Taken together, these interwoven findings suggest that blocking theeffects of PGD2 on DP1 is likely to be undesirable in patients with heart disease , and perhaps in particular, those taking niacin. That possibilityis not addressed by the design of the large ongoing trial of theniacin/DP1 antagonist combination, say the researchers. Should such a hazard exist, FitzGerald expects it to be confined tothose patients not taking low-dose aspirin, along with niacin."This potential hazard of blocking one aspect of PGD2 action, theone dependent on DP1, contrasts nicely with our recent report thatblocking its other receptor, DP2, may be beneficial in limitingmale-pattern baldness " said FitzGerald. Additional References Citations. We are high quality suppliers, our products such as Basket Cable Tray Manufacturer , Wire Cable Tray Manufacturer for oversee buyer. To know more, please visits Wire Storage Cage.
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