Navigation Links
Reducing the Risk of Protease Inhibitor-Related Atherosclerosis

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.

Long-term side effects a concern

Protease inhibitors have been effective in prolonging the lives of people with AIDS, so much so th at 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.



Sourc-Newswise
SRM
'"/>




Related medicine news :

1. Reducing Lung Cancer Risk
2. Reducing the risk for type 2 diabetes
3. Reducing Medication Errors
4. Reducing HIV Transmission
5. Reducing Pain from Knee Surgery
6. Reducing Pain From Knee Surgery
7. Reducing The After Effects of Tonsillectomy
8. Antiparasitic Drug Effective In Reducing Seizures In Neurocysticercosis Patients
9. Reducing Number Of Cigarettes Not Enough
10. Drug Found Effective In Reducing Vertebral Fractures In Women
11. Reducing TB With Ultraviolet Light
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:12/2/2016)... ... 2016 , ... Sourced from the Isbre Springs beneath the 5,000 year old ... purity of just 6 ppm TDS (Total Dissolved Solids) in addition to its excellent ... in several ShopRite and FoodTown stores in NJ and received rave comments from consumers. ...
(Date:12/2/2016)... San Francisco, CA (PRWEB) , ... December 02, ... ... in digitally-enabled care journeys, announced today that it has raised $6.0 million in ... are inspired by Clarify Health’s conviction that patients and their caregivers can receive ...
(Date:12/2/2016)... ... ... ‘Tis the season for giving! Today, 20 creative teams across the nation ... the Drug Enforcement Administration as part of the National Red Ribbon Week Photo Contest. ... decorated their campuses with this year’s Red Ribbon Week theme: “YOLO. Be Drug Free,” ...
(Date:11/30/2016)... ... 2016 , ... Standard Process, Inc. is proud to announce ... of the largest closely held companies headquartered in Wisconsin. This marks the company’s ... Process was awarded the Talent Award for providing outstanding employee benefits. , ...
(Date:11/30/2016)... ... November 30, 2016 , ... The Cronovo Smartwatch, the ... by today’s consumers at an affordable price, is now available on the crowdfunding ... is “a game changer” when it comes to the smartwatch. , "With Cronovo, ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... , December 2, 2016 On ... Committee honored excellence in research, development and innovation in ... gala dinner was held in the presence of Sergey ... Russian Federation , Natalia Sanina, First ... Mikhail Murashko , Head of Roszdravnadzor, National Service of ...
(Date:12/2/2016)... British Columbia , December 2, 2016 bioLytical ... den INSTI HIV-Selbsttest, bei den Mitgliedern des Apothekenbundes von Kenia eingeführt. ... ... INSTI HIV Self Test! (PRNewsFoto/bioLytical Laboratories) ...      (Photo: http://photos.prnewswire.com/prnh/20161201/444905 ) ...
(Date:12/2/2016)... -- Lianluo Smart Limited (Nasdaq: LLIT ... markets and sells medical devices and wearable sleep ... and international markets, recently attended the 2016 Guangdong ... Forum, co-hosted by the Institute of Interventional Cardiology ... Provincial People,s Hospital and Cardiology Department of Guangdong ...
Breaking Medicine Technology: