Navigation Links
New potential drug target for the treatment of atherosclerosis
Date:3/4/2008

LA JOLLA, CA A nuclear receptor protein, known for controlling the ability of cells to burn fat, also exerts powerful anti-inflammatory effects in arteries, suppressing atherosclerosis in mice prone to developing the harmful plaques, according to new research by scientists at the Salk Institute for Biological Studies and the Harvard School of Public Health.

Their findings, reported in this weeks online edition of the Proceedings of the National Academy of Sciences, offer a new and specific target for the development of drugs that specifically treat cardiovascular complications associated with metabolic syndrome.

Heart disease is like a ticking clockit is progressive, relentlessly marching forward accelerated by a mix of high fat diets, inflammation and high blood pressure. We show that PPAR delta offers a kind of genetic shortcut around each of these medical roadblocks, says Howard Hughes Medical Investigator Ronald M. Evans, Ph.D., a professor in the Salk Institutes Gene Expression Laboratory, who co-directed the study with Chih-Hao Lee, a professor in the Department of Genetics and Complex Diseases at the Harvard School of Public Health.

Most people believe cholesterol plays a predominant role in atherosclerosis. Our study suggests that targeting inflammation at lesion sites is just as important, adds Lee.

Like the Yin and Yang of fat metabolism, PPAR delta the focus of the current study and its counterpart PPAR gamma control the storage and burning of fat. PPAR gamma is in charge of storing surplus glucose as fat. When PPAR gamma is stimulated by a drug the bodys response to insulin improves, lowering levels of circulating glucose. Its sibling gene switch, PPAR delta, controls the ability of cells to burn fat. Activating PPAR delta revs up the fat-burning capacity of adipose tissue and muscle, dramatically lowers overall body weight, increases HDL (the good cholesterol), reduces circulating triglycerides, and improves hyperglycemia.

Cardiovascular disease is a leading cause of death in patients with metabolic syndrome, a clustering of obesity-related disorders including insulin resistance, hypertension, and dyslipidemia, says postdoctoral researcher and first author Grant D. Barish, M.D. Since PPAR delta plays a key role in fat metabolism and PPAR delta drugs can protect against obesity, we wanted to know whether activating PPAR delta would protect against atherosclerosis.

Atherosclerosis or hardening of the arteries" is a chronic disease in which high cholesterol levels coupled with inflammation lead to the build-up of fatty deposits, called plaque, on the inner walls of arteries. Eventually these plaques can limit blood flow, leading to angina, or they may rupture, resulting in blood clots that block arteries and cause heart attacks or strokes.

When the researchers fed an experimental drug that turns on PPAR delta to genetically altered mice that develop the characteristic plaques at an early age, especially when placed on a high-fat diet, mice developed 2530 percent fewer plaques. Further studies revealed that PPAR delta not only raises HDL levels but also suppresses the inflammatory response in the artery, dramatically slowing down lesion progression.

Barish and Evans also contributed to a related study, which was led by researchers at the University of California, Los Angeles and published in the same issue of PNAS. Using a different mouse model to mimic the development of atherosclerosis, the UCLA researchers detected an even more pronounced anti-inflammatory effect that slashed the number of aortic lesions by up to 70 percent.

While Barish, a clinically trained endocrinologist, cautions that extrapolating from mice to humans is inherently fraught with complications, he believes that drugs switching on PPAR delta have the potential to protect against obesity, insulin resistance and their associated cardiovascular risks.

The discovery that any orally active compound can delay the progression of heart disease is rare, and considering the importance of the problem, we are hopeful that this work can be quickly carried into the clinic, says Evans.


'/>"/>

Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-410-01340
Salk Institute
Source:Eurekalert  

Related medicine news :

1. Large source of nitrate, a potential water contaminant, found in near-surface desert soils
2. Weill Cornell team identifies potential new drug targets against hormone-dependent breast cancer
3. Alimera Sciences Signs Second Agreement With Emory University for Potential Treatments Using New Class of Antioxidants
4. Researcher of the University of Navarra discovered potential antidepressant compounds
5. Scientists using laser light to detect potential diseases via breath samples, says new study
6. ASAM Calls for Care in the Use of, and the Prescribing of, Potentially Addictive Substances
7. Growing markets bring potential for rubber and oilseed crops
8. Heating Plastic Bottles Releases Potentially Harmful Chemical
9. Hot liquids release potentially harmful chemicals in polycarbonate plastic bottles
10. New nanotube findings by Stanford researchers give boost to potential biomedical applications
11. Battling potential disease outbreaks online
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New potential drug target for the treatment of atherosclerosis
(Date:6/27/2016)... ... June 27, 2016 , ... ... industry today announced its strategic partnership with Connance, a healthcare industry leader ... two companies’ proven, proprietary technology combine to provide health systems, hospitals and ...
(Date:6/26/2016)... ... , ... Quality metrics are proliferating in cancer care, and are derived from ... of the beholder, according to experts who offered insights and commentary in the current ... For the full issue, click here . , For the American Society of ...
(Date:6/26/2016)... ... , ... PawPaws brand pet supplements owned by Whole Health Supply ... health of felines. The formula is all-natural and is made from Chinese herbs that ... Cat Kidney Support Supplement Soft Chews are Astragalus Root Extract and Rehmannia Root ...
(Date:6/25/2016)... ... June 25, 2016 , ... Experts from the ... AcademyHealth’s Annual Research Meeting June 26-28, 2016, at the Hynes Convention Center in ... topics including advance care planning, healthcare costs and patient and family engagement. , ...
(Date:6/25/2016)... ... 2016 , ... "With 30 hand-drawn hand gesture animations, FCPX users can easily ... of Pixel Film Studios. , ProHand Cartoon’s package transforms over 1,300 hand-drawn pictures ... . Simply select a ProHand generator and drag it above media or text in ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016 ... has announced the addition of the " Global ... This report ... provides an updated review, including its applications in various ... total market, which includes three main industries: pharmaceutical and ...
(Date:6/24/2016)... , June 24, 2016 Dehaier Medical Systems ... "Company"), which develops, markets and sells medical devices and ... , signed a strategic cooperation agreement with Hongyuan Supply ... Supply Chain") on June 20, 2016, to develop Dehaier,s ... strategic cooperation agreement, Dehaier will leverage Hongyuan Supply Chain,s ...
(Date:6/24/2016)... , June 24, 2016 According ... by Type (Standard Pen Needles, Safety Pen Needles), Needle ... GLP-1, Growth Hormone), Mode of Purchase (Retail, Non-Retail) - ... This report studies the market for the forecast period ... reach USD 2.81 Billion by 2021 from USD 1.65 ...
Breaking Medicine Technology: