Study shows that blocking an inflammation pathway prevents cardiac fibrosis

March 22, 2013, UC Davis

(Medical Xpress)—New research from UC Davis published in the Proceedings of the National Academy of Sciences shows that blocking an enzyme that promotes inflammation can prevent the tissue damage following a heart attack that often leads to heart failure.

Led by Nipavan Chiamvimonvat, cardiologist and professor of internal medicine, a team of researchers tested a compound that inhibits the enzyme soluble epoxide hydrolase—or sEH—one of the key players in the robust immune-system response that heals tissue following an injury. The enzyme, however, can become counterproductive after a cardiac event.

Chiamvimonvat explained that sEH increases proinflammatory lipid mediators, leading to long-term, heightened . It also causes cells, which typically link together and provide the foundation for tissue, to overwork. The outcome is , or fibrosis, that results in an abnormal relaxation of the heart after each beat, taxing remaining heart muscle as it performs double duty and eventually leading to a decline in the heart's pumping action.

"We often see patients following a in clinic who initially respond well to current treatments, which address the initial causes of the cardiac event and try to preserve heart function," said Chiamvimonvat, whose research focuses on the of heart disease. "Over time, though, in some patients continues to worsen and can lead to . It would be ideal to have new approaches that target the cellular overproduction that leads to heart muscle stiffening and cardiac fibrosis."

Heart failure progressively limits oxygen throughout the body, reducing mobility, respiration and quality of life. According to the Centers for Disease Control and Prevention, the condition affects 5.7 million people in the U.S. and costs the nation $34.4 billion in health-care services, medications and lost productivity. About half of people who have heart failure die within five years of diagnosis.

Previous research by Chiamvimonvat showed that an sEH inhibitor synthesized in the laboratory of entomology Professor Bruce Hammock can reduce the enlargement of cells and associated arrhythmia. For the current study, she conducted a series of experiments to determine if it could also be a potential treatment for fibrosis.

Chiamvimonvat and her team tested the compound on a mouse model for heart attack. Because cardiac fibrosis can also be caused by other long-term cardiac diseases, the compound was also used on a mouse model for the chronic pressure overload commonly seen with hypertension. For both models, one group of mice was given the compound with their drinking water, while another group was not. The animals' heart functions were assessed using echocardiography.

The results showed that the mice receiving treatment had significant decreases in adverse cardiac muscle remodeling following a heart attack or due to chronic pressure overload. Their overall cardiac function also improved. Additional tests performed in Hammock's lab showed significantly reduced inflammatory factors in their systems.

"Our study shines new light on this inflammation pathway and identifies a potential therapeutic target that could greatly expand options for one of the biggest and most difficult-to-treat problems in cardiology," said Javier Lopez, cardiologist, assistant professor of internal medicine and study co-author who developed methods used in the study to quantify fibrotic cells.

The team hopes to test the compound next on a larger animal model as a precursor to human clinical trials.

"This project is part of a long-term, exciting collaboration between two labs dedicated to combining their strengths to benefit human health," said Hammock. "The translational value of our research is significant."

Explore further: Inhibiting CaMKII enzyme activity could lead to new therapies for heart disease

Related Stories

Inhibiting CaMKII enzyme activity could lead to new therapies for heart disease

October 11, 2012
University of Iowa researchers have previously shown that an enzyme called CaM kinase II plays a pivotal role in the death of heart cells following a heart attack or other conditions that damage or stress heart muscle. Loss ...

Thyroid hormones reduce damage and improve heart function after myocardial infarction in rats

February 28, 2013
Thyroid hormone treatment administered to rats at the time of a heart attack (myocardial infarction) led to significant reduction in the loss of heart muscle cells and improvement in heart function, according to a study published ...

Protein linked to increased risk of heart failure and death in older adults

August 29, 2012
A protein known as galectin-3 can identify people at higher risk of heart failure, according to new research supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. This ...

New injectable hydrogel encourages regeneration, improves functionality after heart attack

February 20, 2013
University of California, San Diego bioengineers have demonstrated in a study in pigs that a new injectable hydrogel can repair damage from heart attacks, help the heart grow new tissue and blood vessels, and get the heart ...

Recommended for you

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.