Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New driver of atherosclerosis offers potential as therapeutic target

20.06.2014

A new driver of atherosclerosis has been identified by researchers at UT Southwestern Medical Center. This molecule, known as 27HC (27-hydroxycholesterol), has been found to exacerbate the development of the condition, and may prove to be a promising therapeutic target.

Atherosclerosis is characterized by the build-up of lesions (or plaques) formed from lipids, such as cholesterol and fatty acids. Ruptured plaques can partially or completely block blood flow, potentially leading to a heart attack or stroke. A member of a larger family of molecules known as oxysterols, 27HC is produced during the normal breakdown of cholesterol and is known to accumulate in atherosclerotic plaques.


This is Dr. Shaul,UT Southwestern Medical Center.

Credit: UT Southwestern

The new study, conducted by a team of UT Southwestern researchers led by senior author Dr. Philip Shaul, sought to identify the impact of 27HC on atherosclerosis. Dr. Shaul is Vice Chair for Research and Professor of Pediatrics, and Director of the Center for Pulmonary and Vascular Biology at UT Southwestern. The study's findings – first-authored by Dr. Michihisa Umetani, Assistant Professor of Pediatrics and Pharmacology – were recently published in Cell Metabolism.

Using animal models and other strategies, the researchers found that 27HC promotes the formation of atherosclerotic plaques, causing a doubling in the accumulation of lipids in the arterial wall. 27HC achieves this buildup through mechanisms mediated by estrogen receptors, which normally enable the hormone estrogen to protect against the development and progression of atherosclerosis. By blocking estrogen receptors, 27HC prevents the beneficial effects of estrogen and promotes atherosclerosis.

"When 27HC is present, estrogen's protective effects are only observed at very high levels of the hormone," said Dr. Shaul, holder of the Associates First Capital Corporation Distinguished Chair in Pediatrics. "This result may explain why hormone therapy with estrogen does not provide cardiovascular benefit in women with pre-existing atherosclerosis, in which 27HC is abundant in the vascular wall."

Probing further into the underlying mechanisms, the researchers discovered that 27HC triggers inflammation in the arterial wall, a key step in the establishment of atherosclerotic plaques. This detrimental effect was characterized by exaggerated production of molecules that drive inflammation, called cytokines, and enhanced attachment on the arterial wall of immune cells known as macrophages. It is the recruitment of macrophages that then accumulate lipids (such as cholesterol) that triggers the formation of atherosclerotic plaques.

"Although statins have had a dramatic impact on cardiovascular health by lowering cholesterol, we still need complementary methods to combat atherosclerosis," Dr. Shaul said. "Targeting 27HC, either by lowering the levels of this compound or by inhibiting its actions, could potentially provide a complementary approach to preventing vascular disease."

###

Other UT Southwestern researchers involved in the study include Dr. Pritam Ghosh, Assistant Professor of Internal Medicine; Dr. Tomonori Ishikawa, postdoctoral research fellow in Pediatrics; Dr. Chieko Mineo, Associate Professor of Pediatrics; and Junko Umetani and Mohamed Ahmed, research assistants in Pediatrics.

The study was funded by support from the National Institutes of Health, the American Diabetes Association, and an unrestricted endowment provided to Dr. Shaul by the Associates First Capital Corporation.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 91,000 hospitalized patients and oversee more than 2 million outpatient visits a year.

Remekca Owens | Eurek Alert!

Further reports about: atherosclerosis cholesterol hormone inflammation levels macrophages vascular

More articles from Health and Medicine:

nachricht Mobile phone test can reveal vision problems in time
11.02.2016 | University of Gothenburg

nachricht Proteomics and precision medicine
08.02.2016 | University of Iowa Health Care

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: Production of an AIDS vaccine in algae

Today, plants and microorganisms are heavily used for the production of medicinal products. The production of biopharmaceuticals in plants, also referred to as “Molecular Pharming”, represents a continuously growing field of plant biotechnology. Preferred host organisms include yeast and crop plants, such as maize and potato – plants with high demands. With the help of a special algal strain, the research team of Prof. Ralph Bock at the Max Planck Institute of Molecular Plant Physiology in Potsdam strives to develop a more efficient and resource-saving system for the production of medicines and vaccines. They tested its practicality by synthesizing a component of a potential AIDS vaccine.

The use of plants and microorganisms to produce pharmaceuticals is nothing new. In 1982, bacteria were genetically modified to produce human insulin, a drug...

Im Focus: The most accurate optical single-ion clock worldwide

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock which attains an accuracy which had only been predicted theoretically so far. Their optical ytterbium clock achieved a relative systematic measurement uncertainty of 3 E-18. The results have been published in the current issue of the scientific journal "Physical Review Letters".

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock...

Im Focus: Goodbye ground control: autonomous nanosatellites

The University of Würzburg has two new space projects in the pipeline which are concerned with the observation of planets and autonomous fault correction aboard satellites. The German Federal Ministry of Economic Affairs and Energy funds the projects with around 1.6 million euros.

Detecting tornadoes that sweep across Mars. Discovering meteors that fall to Earth. Investigating strange lightning that flashes from Earth's atmosphere into...

Im Focus: Flow phenomena on solid surfaces: Physicists highlight key role played by boundary layer velocity

Physicists from Saarland University and the ESPCI in Paris have shown how liquids on solid surfaces can be made to slide over the surface a bit like a bobsleigh on ice. The key is to apply a coating at the boundary between the liquid and the surface that induces the liquid to slip. This results in an increase in the average flow velocity of the liquid and its throughput. This was demonstrated by studying the behaviour of droplets on surfaces with different coatings as they evolved into the equilibrium state. The results could prove useful in optimizing industrial processes, such as the extrusion of plastics.

The study has been published in the respected academic journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).

Im Focus: New study: How stable is the West Antarctic Ice Sheet?

Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels

A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Symposium on Climate Change Adaptation in Africa 2016

12.02.2016 | Event News

Travel grants available: Meet the world’s most proficient mathematicians and computer scientists

09.02.2016 | Event News

AKL’16: Experience Laser Technology Live in Europe´s Largest Laser Application Center!

02.02.2016 | Event News

 
Latest News

Graphene leans on glass to advance electronics

12.02.2016 | Materials Sciences

Twisting magnets enhance data storage capacity

12.02.2016 | Materials Sciences

A metal that behaves like water

12.02.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>