![]() ![]() The researchers suggest that these findings are reflective of DP1 expression 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 that niacin evoked COX-1- dependent formation of both TxA2 and PGD2 in platelets and that a DP1 blockade enhanced the effect of TxA2 on platelet activation. ![]() However, deletion of DP1 made mice somewhat more susceptible to hardening of the arteries, the formation of aneurysm, thrombosis, and in some cases, high blood pressure. “Frankly, because of this, we did not expect to detect any signal of cardiovascular hazard in the mice,” notes senior author Garret FitzGerald, MD, director of the Institute for Translational Medicine and Therapeutics. However, unlike humans, mice do not express DP1 in their platelets. ![]() As low-dose aspirin is cardioprotective by thinning blood, the benefit from shutting down platelet TxA2 trumps the potential risk of suppressing platelet PGD2 production.To gather more information on the potential risks from blocking DP1, the Penn investigators used mice lacking the DP1 receptor. This is surprising as PGD2 is made in platelets by COX-1, the target inhibited by low-dose aspirin.ĬOX-1 in platelets also makes thromboxane (Tx)A2, another fat that activates platelets. In work published in the Journal of Clinical Investigation this month, first authors Wenliang Song, MD, research assistant professor, and Jane Stubbe, PhD, postdoctoral fellow, in the Perelman School of Medicine, University of Pennsylvania, and their colleagues now question the wisdom of blocking DP1 in patients prone to cardiovascular disease, especially those taking niacin.ĭrawing evidence from studies in mice and humans, they show that platelets - complicated cells circulating in the bloodstream that stick together in the first phase of blood clotting - make PGD2, which acts as a brake via DP1 on their own activation. In fact, a combination of a DP1- blocking drug and niacin is being evaluated in a large clinical trial to determine its effectiveness in reducing heart attacks, as opposed to other drugs that reduce LDL cholesterol. PGD2, formed by an enzyme called COX-2 and released by immune and skin cells, acts on a muscle cell-surface receptor called DP1 to cause the flushing. PGD2 is the primary cause of the unwanted vasodilation, the “niacin flush.” The dilation occurs when blood vessels widen from relaxed smooth muscle cells within vessel walls. Patients often stop taking niacin because it causes uncomfortable facial flushing, an effect caused by the release of a fat called prostaglandin or (PG)D2. Niacin keeps fat from breaking down, and so obstructs the availability of LDL building blocks. Newswise - PHILADELPHIA - 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 much attention from patients and physicians. ![]()
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