Nav: Home

Researchers reveal key role of pressure-sensing protein in lung edema

June 11, 2019

Researchers at the University of Illinois at Chicago describe for the first time the role of a unique, pressure-sensing protein in the development of lung edema -- a condition in which chronic high vascular pressure in the lungs causes fluid from the bloodstream to enter the air spaces of the lungs.

The results, which are published in the Proceedings of the National Academy of Sciences, suggest that suppressing the activity of the protein could be a new approach to treating lung edema.

Lung edema can have a variety of causes, including heart failure. Certain types of heart failure -- where the heart is chronically unable to pump blood efficiently -- can cause increased pressure in the blood vessels in the lungs. The high pressure can result in capillary stress failure, where connections between the individual cells that make up the walls of the capillary blood vessels become looser, allowing fluid from the bloodstream to enter the air spaces in the lungs.

Yulia Komarova, UIC associate professor of pharmacology, and Asrar Malik, Schweppe Family Distinguished Professor and head of pharmacology in the UIC College of Medicine, have been studying adherens junctions -- the structures that bind together the cells that make up blood vessels. Adherens junctions act like adjustable nuts and bolts that can be tightened or loosened to modulate the flow of fluids and blood cells into and out of the bloodstream, such as immune cells that travel in the blood to get to areas where they are needed.

Komarova and colleagues wanted to see if a protein called piezo 1 -- which is found in many cell types, including in the endothelial cells that line the blood vessels, and that can sense mechanical pressure -- was involved in triggering adherens junctions to loosen up under conditions of high fluid pressure in the lungs.

The researchers engineered mice where piezo 1 was deleted in the adult animal in the endothelial cells. They then elevated the pressure in blood vessels in the lungs in order to mimic the effects of heart failure. In mice where piezo 1 was deleted in the endothelial cells, minimal fluid was seen entering the lungs, while in mice that had the piezo 1 protein, the lungs filled with fluid as blood pressure increased.

In a separate experiment, Komarova and colleagues used a mouse model where the adherens junctions were artificially reinforced in endothelial cells to keep the connections between individual cells lining the blood vessel cells tight. In these mice, no fluid was seen to enter the lungs when high pressures were induced in the animals even when they had the piezo 1 protein.

"Our experiments suggest that by either blocking the activity of piezo 1 or by bolstering the adherens junctions we can prevent fluid from entering the lungs," Komarova said. "Small drug molecules that achieve these goals could represent novel therapeutic approaches to treat lung edema associated with heart failure."
-end-
Emily Friedrich, Zhigang Hong, Shiqin Xiong, Ming Zhong, Anke Di, Jalees Rehman are co-authors on the paper.

This research was supported by grants T32HL007829 and R01HL045638 from the National Institutes of Health.

University of Illinois at Chicago

Related Heart Failure Articles:

Type 2 diabetes may affect heart structure and increase complications and death among heart failure patients of Asian ethnicity
The combination of heart failure and Type 2 diabetes can lead to structural changes in the heart, poorer quality of life and increased risk of death, according to a multi-country study in Asia.
Preventive drug therapy may increase right-sided heart failure risk in patients who receive heart devices
Patients treated preemptively with drugs to reduce the risk of right-sided heart failure after heart device implantation may experience the opposite effect and develop heart failure and post-operative bleeding more often than patients not receiving the drugs.
How the enzyme lipoxygenase drives heart failure after heart attacks
Heart failure after a heart attack is a global epidemic leading to heart failure pathology.
Novel heart pump shows superior outcomes in advanced heart failure
Severely ill patients with advanced heart failure who received a novel heart pump -- the HeartMate 3 left ventricular assist device (LVAD) -- suffered significantly fewer strokes, pump-related blood clots and bleeding episodes after two years, compared with similar patients who received an older, more established pump, according to research presented at the American College of Cardiology's 68th Annual Scientific Session.
NSAID impairs immune response in heart failure, worsens heart and kidney damage
Non-steroidal anti-inflammatory drugs, or NSAIDs, are widely known as pain-killers and can relieve pain and inflammation.
Heart cell defect identified as possible cause of heart failure in pregnancy
A new Tel Aviv University study reveals that one of the possible primary causes of heart failure in pregnant women is a functional heart cell defect.
In heart failure, a stronger heart could spell worse symptoms
Patients with stronger-pumping hearts have as many physical and cognitive impairments as those with weaker hearts, suggesting the need for better treatment.
Patients with common heart failure more likely to have lethal heart rhythms
New Smidt Heart Institute Research shows that patients with Heart Failure with Preserved Ejection Fraction (HFpEF) are more likely to have lethal heart rhythms.
Why does diabetes cause heart failure?
A Loyola University Chicago Stritch School of Medicine study reveals how, on a cellular level, diabetes can cause heart failure.
Oxygen therapy for patients suffering from a heart attack does not prevent heart failure
Oxygen therapy does not prevent the development of heart failure.
More Heart Failure News and Heart Failure Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.