Scientists demonstrate a new mechanism of atherosclerosis in mice increased

For all the good it does, a liver protein that detects and drugs and remove pollutants from the body, has a drawback. For the first time has shown that when it is chronically activated, the protein called PXR, rejiggers how cholesterol is processed in the liver and increases the risk of atherosclerosis. The work has direct clinical implications for patients on long-term treatment of PXR-activating drugs, including certain antibiotics and drugs against cancer - and your daily latte.

A shot of espresso, you can rev up in the morning, but the drawback is that it can ramp rates "bad" cholesterol because its effects on the liver is a unique protein called PXR. New research from Rockefeller University has now shown that in chronically activated rejiggers the protein is broken down and dismantled, such as cholesterol in the liver, a disease with a high concentration of waxy substance or worse atherosclerosis can be cultivated.

"Who is the first time that PXR has had a direct influence on the balance of cholesterol in the body," says Zhou Changcheng first author, research associate in January Breslow L. 's Laboratory of Biochemical Genetics and Metabolism at Rockefeller.

Unlike other receptor proteins that are only one or a few chemicals, PXR - short for pregnane X receptor - over a hundred of them can detect cafestrol detect the presence of unfiltered coffee, and a number of drugs prescription. The research that has resulted from Breslow carbamazipine can direct clinical implications for patients with drugs such as rifampicin, an antibiotic in the treatment of tuberculosis, ritonavir antiretroviral drugs for HIV treatment and anti-epileptics, phenobarbital, turn on all the PXR.

"As these drugs have been developed - antivirals, antibiotics, anti-cancer supplements and herbal like St. John's - their interactions with PXR was not known," said Zhou. "Now, Patients on long-term treatment with drugs activating PXR-can learn more about the effects of these drugs can be informed. "

If this function is activated, PXR, which is located in the nucleus of liver cells in all animals, including humans, the locks on the bands of DNA and turns on genes, such as chemicals or drugs are metabolized and excreted by the liver to regulate. To find many drugs that activate PXR proven to raise cholesterol levels of patients, and too much in your blood is an established risk factor for cardiovascular disease, the leading cause of mortality in the nation. However, it was not clear whether this process could start-PXR. In their work, Zhou and Breslow, a specific mouse PXR activator PCN has been called in the diet of normal mice for two weeks and found that while values were good or HDL cholesterol is not affected if the level of bad cholesterol level increased six fold -. Another group of mice that were fed for eight weeks and the NCP have been genetically devoid of the protein ApoE developed showed the decline: the good cholesterol has dropped and they also went to the development of atherosclerosis in adults.

Several target genes of PXR were the same for both normal mice and those without the ApoE protein, including an enzyme called cholesterol metabolism and transport of CYP39A1 protein called Apo-IV. A gene called CD36, is another target specifically with the inclusion of "bad" cholesterol, by certain cells that contribute to clogged arteries, accumulation of fat attached.

To Zhou, this research is only the beginning. "Many are exposed to chemicals in the air, such as PXR activators, said Zhou. "What we have in our hands can now not only heart health but also a public health problem."