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:2/10/2016)... ... ... Emergency rooms provide emergency care to stabilize critical health issues, but emergency ... emergencies at risk of losing a tooth or their smiles. Dr. Marine Martirosyan, ... emergencies include:, , Avulsed or knocked-out teeth , ...
(Date:2/10/2016)... ... February 10, 2016 , ... ... bring together more than 200 of the country’s top healthcare executives to share ... “The true benefit of the Forum is the provider-centric perspective, experience, expertise and ...
(Date:2/10/2016)... ... February 10, 2016 , ... AHRA: The ... and inspirational speaker Jan Fox will serve as keynote speaker at the organization’s ... participants with tools to more effectively communicate with their own organizational staff and ...
(Date:2/10/2016)... ... February 10, 2016 , ... ... digital self-scheduling readily available to physicians. The integration will enable Allscripts users ... select appointments via Everseat’s free mobile app. , The partnership gives Everseat substantial ...
(Date:2/10/2016)... , ... February 10, 2016 , ... The recreational use ... enthusiasts in the state still face a lot of restrictions as to where they ... intended for private, personal use” and that cannabis “may not be consumed openly or ...
Breaking Medicine News(10 mins):
(Date:2/10/2016)... 2016 CSI Specialty Group (CSI) expanded its ... the Specialty Pharmacy Podcast. A free, weekly show, the ... real-world education, discussion and context amongst specialty pharmacy peers ... --> The Specialty Pharmacy Podcast, hosted by ... Group Suzette DiMascio, CHE, CMCE, CPC, is available for ...
(Date:2/10/2016)... Switzerland and SAN DIEGO ... , Inc., a global leader in viral gene therapy ... therapy treatments for congestive heart failure and other chronic ... develop a scalable manufacturing process and produce cGMP-grade RT-100 ... trials. --> --> ...
(Date:2/10/2016)... Feb. 10, 2016 Urologix, the market leader ... of Benign Prostatic Hyperplasia (BPH), announces new private ownership ... , a medical device industry veteran of more than ... Liability Company.  Plymouth, Minn. ... Cooled ThermoTherapy™ and Prostiva® RF Therapy, will continue to ...
Breaking Medicine Technology: