New study cautions use of drugs to block 'niacin flush'
April 9, 2012 in Medical research
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. Niacin keeps fat from breaking down, and so obstructs the availability of LDL building blocks.
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. 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.
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. 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.
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.
Drawing 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. This is surprising as PGD2 is made in platelets by COX-1, the target inhibited by low-dose aspirin.
COX-1 in platelets also makes thromboxane (Tx)A2, another fat that activates 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. However, unlike humans, mice do not express DP1 in their platelets. "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, 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. 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.
Taken together, these interwoven findings suggest that blocking the effects of PGD2 on DP1 is likely to be undesirable in patients with heart disease, and perhaps in particular, those taking niacin. That possibility is not addressed by the design of the large ongoing trial of the niacin/DP1 antagonist combination, say the researchers.
Should such a hazard exist, FitzGerald expects it to be confined to those patients not taking low-dose aspirin, along with niacin. "This potential hazard of blocking one aspect of PGD2 action, the one dependent on DP1, contrasts nicely with our recent report that blocking its other receptor, DP2, may be beneficial in limiting male-pattern baldness" said FitzGerald.
Provided by
University of Pennsylvania School of Medicine
-
NIH stops study of niacin to prevent heart attacks
May 26, 2011 |
not rated yet |
0
-
Niacin does not reduce heart attack, stroke risk in stable CV patients
Nov 15, 2011 |
not rated yet |
0
-
Research identifies inhibitor causing male pattern baldness and target for hair-loss treatments
Mar 21, 2012 |
not rated yet |
0
-
How niacin fights high cholesterol: New research gets to the heart of the problem
Oct 08, 2010 |
not rated yet |
0
-
Method for manufacturing patient-specific human platelets
Nov 22, 2010 |
not rated yet |
0
-
Motion perception revisited: High Phi effect challenges established motion perception assumptions
Apr 23, 2013 |
3 / 5 (2) |
2
-
Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update)
Apr 02, 2013 |
4.5 / 5 (11) |
5
-
The visual system as economist: Neural resource allocation in visual adaptation
Mar 30, 2013 |
5 / 5 (2) |
9
-
Separate lives: Neuronal and organismal lifespans decoupled
Mar 27, 2013 |
4.9 / 5 (8) |
0
-
Sizing things up: The evolutionary neurobiology of scale invariance
Feb 28, 2013 |
4.8 / 5 (10) |
14
-
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013
-
If you became brain-dead, would you want them to pull the plug?
May 17, 2013
-
MRI bill question
May 15, 2013
-
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013
-
Alcohol and acetaminophen
May 13, 2013
-
Marie Curie's leukemia
May 13, 2013
- More from Physics Forums - Medical Sciences
More news stories
New study finds blind people have the potential to use their 'inner bat' to locate objects
New research from the University of Southampton has shown that blind and visually impaired people have the potential to use echolocation, similar to that used by bats and dolphins, to determine the location of an object.
Medical research
46 minutes ago |
not rated yet |
0
|
Germ-fighting vaccine system makes great strides in delivery
A novel vaccine study from South Dakota State University (SDSU) will headline the groundbreaking research that will be unveiled at the American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference ...
Medical research
1 hour ago |
not rated yet |
0
Discovery of novel medicine for treatment of chronic wounds
Every 20 seconds, a limb is lost as a consequence of diabetic foot ulcer that does not heal. To date, medical solutions that can change this situation are very limited. In his doctoral thesis Yue Shen from the Industrial ...
Medical research
5 hours ago |
not rated yet |
0
Lymphatic fluid takes detour
When tumours metastasise, they can block lymphatic vessels, as researchers from ETH Zurich have discovered using a new method. The lymphatic fluid subsequently has to find a new path through the tissue. Such ...
Medical research
5 hours ago |
not rated yet |
0
|
Computational tool translates complex data into simplified 2-dimensional images
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
Medical research
23 hours ago |
5 / 5 (3) |
0
|
Researchers find far-reaching, microvascular damage in uninjured side of brain after stroke
While the effects of acute stroke have been widely studied, brain damage during the subacute phase of stroke has been a neglected area of research. Now, a new study by the University of South Florida reports that within a ...
Breakup of physician, drug company relationship could improve health care, cut cost
A new report suggests that improved health care and significant reductions in drug costs might be attained by breaking up the age-old relationship between physicians and drug company representatives who promote the newest, ...
Food laboratory accuracy remains a concern
Food microbiology laboratories continue to submit false negative results and false positive results on a routine basis. A retrospective study of nearly 40,000 proficiency test results over the past 14 years, presented today ...
Study supports 'aggressive' treatment for posterior fossa hematoma in newborns
Posterior fossa subdural hematoma (PFSDH) is a serious and rare condition in newborns, generally occurring after difficult deliveries. But with appropriate treatment, there's an excellent chance of good long-term outcomes ...
Which women should be screened for high cholesterol?
National guidelines recommend that at-risk women be screened for elevated cholesterol levels to reduce their chances of developing cardiovascular disease. But who is 'at risk?' The results of a study by investigators ...
First long-term study reveals link between childhood ADHD and obesity
A new study conducted by researchers at the Child Study Center at NYU Langone Medical Center found men diagnosed as children with attention-deficit/hyperactivity disorder (ADHD) were twice as likely to be obese in a 33-year ...