Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Drug combo may reduce protease inhibitor-related hardening of the arteries

Physiologists may have found a way to decrease the risk of hardening of the arteries that accompanies the long-term use of protease inhibitors, a class of drugs that has emerged as the most effective treatment against HIV and AIDS.

Writing in the American Journal of Physiology–Cell Physiology, researchers from the University of Kentucky found that when mice were given a nucleoside reverse transcriptase inhibitor (NRTI) and a protease inhibitor in combination, it prevented hardening of the arteries often associated with long-term use of protease inhibitors alone. The mice received ritonavir, a common protease inhibitor, in combination with d4T or didanosine, which are common NRTIs.

"The combination prevented the negative cardiovascular effect, hardening of the arteries, of the protease inhibitors without reducing the effectiveness of the protease inhibitors on HIV," said the study's senior author, Eric J. Smart. "To our knowledge, these are the first data that indicate that nucleoside reverse transcriptase inhibitors can limit the atherogenic (tendency to form lipid deposits in the arteries) effects of ritonavir," the authors wrote.

The study also found:

• Although protease inhibitors alone caused cholesterol to build up in mouse arteries, the increased cholesterol could not be detected in the blood. "This means that when doctors test for cholesterol on human patients who are using protease inhibitors, their cholesterol levels may look normal even when they are not," Smart said. "In other words, the accumulation of cholesterol within the arteries is a silent problem."

• Although Vitamin E, an antioxidant, has been shown to prevent the negative effects of protease inhibitors in vitro (in the test tube), the vitamin provided no benefit to the mice in this study.

The study, entitled "Nucleoside reverse transcriptase inhibitors prevent HIV protease inhibitor-induced atherosclerosis by ubiquitination and degradation of protein kinase C," was carried out by Emily L. Bradshaw, Xian-An Li, Theresa Guerin, William V. Everson, Melinda E. Wilson, Annadora J. Bruce-Keller, Richard N. Greenberg, Ling Guo, Stuart A. Ross and Eric J. Smart. The researchers are from the University of Kentucky and the Veterans Administration Medical Center in Lexington. The American Physiological Society published the study.

Long-term side effects a concern

Protease inhibitors have been effective in prolonging the lives of people with AIDS, so much so that patients now survive long enough to develop side effects that are years in the making. One such side effect is atherosclerosis, the accumulation of cholesterol and foam cells in the arteries, causing the vessels to narrow and harden.

Atherosclerosis is a problem in the general population, but protease inhibitors accelerate the process by increasing production of the protein CD36 within macrophages, which fight infections by consuming unwanted materials. CD36 spurs macrophages to eat cholesterol: The more CD36 the body produces, the more cholesterol the macrophages consume.

The problem occurs when cholesterol-laden macrophages get stuck in artery walls. Over time, they accumulate, block the arteries and can result in heart attacks. Because protease inhibitors prompt the CD36-rich macrophages to accumulate more cholesterol, the cholesterol and foam cells build faster and thus lead the arteries to harden more quickly, Smart explained.

Ritonavir produces greater blockage

The researchers examined macrophages isolated from mice receiving ritonavir, a protease inhibitor, and d4T and didanosine, both NRTIs. "NRTIs completely prevented the upregulation of CD36 and the development of atherosclerosis," the authors wrote. Their results also suggest that the NRTIs prevented the increase in CD36 by decreasing protein kinase C, an enzyme that changes the function of proteins.

What's more, NRTI reduced the negative effect of macrophages and cholesterol without reducing the effectiveness that ritonavir had against HIV. "So by giving both drugs at the same time, you get the positive effects of the protease inhibitors without the negative effect of hardening of the arteries," Smart concluded.

The researchers are now beginning a short-term study with healthy human volunteers to see if the protease inhibitor/NRTI drug combination will help control the production of CD36 in humans as well, Smart said.

"We'll try to find out if the NRTI regimen can keep the CD-36 protein in check in the non-infected volunteers," Smart said. If the drug combination works, the researchers will move to further clinical trials.

Christine Guilfoy | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>