Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein in 'good cholesterol' may be a key to treating pulmonary hypertension

28.08.2014

Oxidized lipids are known to play a key role in inflaming blood vessels and hardening arteries, which causes diseases like atherosclerosis.

A new study at UCLA demonstrates that they may also contribute to pulmonary hypertension, a serious lung disease that narrows the small blood vessels in the lungs.


This images shows the differences in the structure of a small lung artery (top row) and heart cross section (lower row) of rodents without disease (far left column); with pulmonary hypertension (middle) and a diseased rodent (left) treated with the HDL peptide. Note the very narrowed lung artery, and thick walls and larger chamber of the right heart in the diseased animal and improvements with 4F peptide treatment.

Credit: UCLA


This image shows the differences in the structure of a small lung artery (top row) and heart (lower row) of rodents without disease (far left column); with pulmonary hypertension (middle) and a diseased rodent (right) treated with the molecule microRNA193. Note the very narrowed lung artery, and thick walls and larger chamber of the heart in the diseased animal and improvements with microRNA-193 treatment.

Credit: UCLA

Using a rodent model, the researchers showed that a peptide mimicking part of the main protein in high-density lipoprotein (HDL), the so-called "good" cholesterol, may help reduce the production of oxidized lipids in pulmonary hypertension. They also found that reducing the amount of oxidized lipids improved the rodents' heart and lung function.

The study appears in the current online edition of the peer-reviewed journal Circulation.

A rare progressive condition, pulmonary hypertension can affect people of all ages. The disease makes it harder for the heart to pump blood through these vital organs, which can lead to heart failure.

"Our research helps unravel the mechanisms involved in the development of pulmonary hypertension," said Dr. Mansoureh Eghbali, the study's senior author and an associate professor of anesthesiology at the David Geffen School of Medicine at UCLA. "A key peptide related to HDL cholesterol that can help reduce these oxidized lipids may provide a new target for treatment development."

Lipids such as fatty acids become oxidized when they are exposed to free radicals — tiny particles that are produced when the body converts food into energy -- or when they are exposed to pollution, and in numerous other ways.

Although researchers have known that oxidized lipids played a role in the development of atherosclerosis and other vascular diseases, the UCLA team discovered higher-than-normal levels of oxidized proteins in rodents with pulmonary hypertension.

The UCLA researchers also knew that apoA-1, a protein that is a key component of HDL cholesterol, can reduce oxidized lipids, so they used a small peptide called 4F that mimics the action of apoA-1 and found that the 4F not only decreased the levels of oxidized lipids in the rodents, but also improved their heart and lung function. Specifically, the peptide restored the altered expression of a key molecule called micro ribonucleic acid (microRNA-193), which targets the action of essential enzymes involved in the production of oxidized lipids.

"The increased amounts of these oxidized lipids due to pulmonary hypertension keeps the expression of this molecule under check, which aggravates symptoms of the disease," said first author Dr. Salil Sharma, a UCLA postdoctoral researcher in anesthesiology.

By restoring the expression of microRNA-193 to its full potential, the researchers reduced the amount of oxidized lipids in the animals with pulmonary hypertension.

One of the hallmarks of pulmonary hypertension is a proliferation of smooth muscle cells in the lungs, which is harmful because it narrows the lungs' small blood vessels.

Additionally, Eghbali's team found reduced levels of microRNA-193 in the blood and lung tissue of human patients with the disease and discovered that they could slow the proliferation of the smooth muscle cells by increasing levels of microRNA-193 in the cells that had been isolated from these patients' lungs.

Further research will be required to test the potential of the HDL-related peptide and microRNA-193 in human disease, and to better understand how the levels of oxidized lipids in the blood may correlate to disease severity in people with pulmonary arterial hypertension.

###

The study was funded in part by the American Heart Association, the National Institute of Health, the UCLA Clinical and Translational Science Institute and the Iris Cantor–UCLA Women's Health Center executive advisory board.

The study's other authors were Dr. Soban Umar, Andrea Iorga, Gabriel Wong, Denise Mai and Dr. Kaveh Navab of the division of molecular medicine at UCLA's department of anesthesiology; David Meriwether, Dr. Mohamad Navab, Dr. Alan Fogelman and Dr. Srinivasa Reddy of the division of cardiology at UCLA's department of medicine; Dr. David Ross of the division of pulmonary critical care medicine at the David Geffen School of Medicine at UCLA's department of medicine; and Francois Potus, Sandra Breuils-Bonnet, Dr. Steve Provencher and Dr. Sébastien Bonnet of Laval University in Québec, Canada.

All of the intellectual property for the HDL-related peptide is owned by the University of California Regents and managed by the UCLA Office of Intellectual Property and Industry Sponsored Research. The technology is currently licensed exclusively to Bruin Pharma Inc. Fogelman, Navab and Reddy are principals in Bruin Pharma, and Fogelman is an officer in the company. Other disclosures are listed in the manuscript.

Rachel Champeau | Eurek Alert!
Further information:
http://www.uclahealth.org/

Further reports about: HDL Health Medicine Protein UCLA blood cholesterol hypertension lung pulmonary

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: Automated driving: Steering without limits

OmniSteer project to increase automobiles’ urban maneuverability begins with a € 3.4 million budget

Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...

Im Focus: Microscopy: Nine at one blow

Advance in biomedical imaging: The University of Würzburg's Biocenter has enhanced fluorescence microscopy to label and visualise up to nine different cell structures simultaneously.

Fluorescence microscopy allows researchers to visualise biomolecules in cells. They label the molecules using fluorescent probes, excite them with light and...

Im Focus: NASA's ICESat-2 equipped with unique 3-D manufactured part

NASA's follow-on to the successful ICESat mission will employ a never-before-flown technique for determining the topography of ice sheets and the thickness of sea ice, but that won't be the only first for this mission.

Slated for launch in 2018, NASA's Ice, Cloud and land Elevation Satellite-2 (ICESat-2) also will carry a 3-D printed part made of polyetherketoneketone (PEKK),...

Im Focus: Sinking islands: Does the rise of sea level endanger the Takuu Atoll in the Pacific?

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister picture is being painted evoking the demise of the island states and their cultures. Are the effects of sea-level rise already noticeable on reef islands? Scientists from the ZMT have now answered this question for the Takuu Atoll, a group of Pacific islands, located northeast of Papua New Guinea.

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister...

Im Focus: Energy-saving minicomputers for the ‘Internet of Things’

The ‘Internet of Things’ is growing rapidly. Mobile phones, washing machines and the milk bottle in the fridge: the idea is that minicomputers connected to these will be able to process information, receive and send data. This requires electrical power. Transistors that are capable of switching information with a single electron use far less power than field effect transistors that are commonly used in computers. However, these innovative electronic switches do not yet work at room temperature. Scientists working on the new EU research project ‘Ions4Set’ intend to change this. The program will be launched on February 1. It is coordinated by the Helmholtz-Zentrum Dresden-Rossendorf (HZDR).

“Billions of tiny computers will in future communicate with each other via the Internet or locally. Yet power consumption currently remains a great obstacle”,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

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

02.02.2016 | Event News

From intelligent knee braces to anti-theft backpacks

26.01.2016 | Event News

DATE 2016 Highlighting Automotive and Secure Systems

26.01.2016 | Event News

 
Latest News

A new potential biomarker for cancer imaging

05.02.2016 | Life Sciences

Graphene is strong, but is it tough?

05.02.2016 | Materials Sciences

Tiniest Particles Shrink Before Exploding When Hit With SLAC's X-ray Laser

05.02.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>