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.
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.
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!
An ounce of prevention: Research advances on 'scourge' of transplant wards
28.08.2015 | University of Wisconsin-Madison
Hypoallergenic parks: Coming soon?
27.08.2015 | American Society of Agronomy
A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.
The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...
A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).
Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...
In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.
These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...
Bacteria do not cease to amaze us with their survival strategies. A research team from the University of Basel's Biozentrum has now discovered how bacteria enter a sleep mode using a so-called FIC toxin. In the current issue of “Cell Reports”, the scientists describe the mechanism of action and also explain why their discovery provides new insights into the evolution of pathogens.
For many poisons there are antidotes which neutralize their toxic effect. Toxin-antitoxin systems in bacteria work in a similar manner: As long as a cell...
It comes when called, bringing care utensils with it and recording how they are used: Fraunhofer IPA is developing an intelligent care cart that provides care staff with physical and informational support in their day-to-day work. The scientists at Fraunhofer IPA have now completed a first prototype. In doing so, they are continuing in their efforts to improve working conditions in the care sector and are developing solutions designed to address the challenges of demographic change.
Technical assistance systems can improve the difficult working conditions in residential nursing homes and hospitals by helping the staff in their work and...
20.08.2015 | Event News
20.08.2015 | Event News
19.08.2015 | Event News
28.08.2015 | Physics and Astronomy
28.08.2015 | Health and Medicine
28.08.2015 | Life Sciences