Nav: Home

Muscle protein abundant in the heart plays key role in blood clotting during heart attack

April 02, 2020

LA JOLLA, CA -- A prevalent heart protein known as cardiac myosin, which is released into the body when a person suffers a heart attack, can cause blood to thicken or clot--worsening damage to heart tissue, a new study shows.

A team led by John H. Griffin, PhD, a professor in the Department of Molecular Medicine at Scripps Research, made the unexpected finding after a series of experiments spanning three years and involving researchers from multiple collaborating institutions.

Though blood clotting is the root cause of many life-threatening cardiac events, including heart attack and stroke, scientists didn't know until now that cardiac myosin was implicated in that process. The protein's primary job is to provide the muscle-motor action that pumps blood.

"The real breakthrough of this study is that we've discovered another major biologic activity of cardiac myosin. No one had suspected it was acting as a procoagulant factor," Griffin says. "Our findings bridge research in hematology and cardiology, showing there's another potentially very important factor influencing the health outcomes of people with cardiac disease."

Blood coagulation is essential to prevent bleeding after an injury. The most abundant procoagulant protein in the human body is collagen, but it's not usually exposed to blood. Upon blood vessel and tissue damage, many procoagulant factors, including collagens, cause blood to turn from a liquid into a gel, forming a blood clot and reducing blood loss. However, procoagulants must strike the right balance between stopping bleeding and preventing excessive clotting, as occurs in conditions such as deep vein thrombosis or when a blood clot causes a stoke.

"Just as with inflammation, a little coagulation is good, but too much is dangerous," Griffin says. "While a small amount of cardiac myosin might help reduce bleeding in the heart, an excess of the protein may worsen the injury by promoting blood clots that cut off oxygen and exacerbate damage to heart tissue."

Indeed, Griffin and his collaborators, including Tobias Eckle, MD, PhD, of the University of Colorado, found that excess cardiac myosin doubled heart damage when administered to mice who experienced controlled heart attacks.

The study appears in the April 2020 issue of the American Heart Association journal Arteriosclerosis, Thrombosis, and Vascular Biology.

Griffin and his team are now working with scientists at Calibr, the drug discovery and development division of Scripps Research, to create a therapeutic compound that would target the procoagulant activity of cardiac myosin, reducing tissue damage caused by a heart attack.

Anticoagulant drugs already exist, ranging from over-the-counter medications like aspirin to widely prescribed drugs such as coumadin and warfarin. A newer class of drugs, known as direct oral anticoagulants (commonly referred to as DOACs), also have emerged to address the great need for blood clotting medications. But many of these existing drugs can cause excessive bleeding or other side effects because they act on the entire body's coagulation system, not just blood clotting in the heart.

Griffin envisions an anticoagulant medicine that targets only cardiac myosin-driven coagulation. Such a drug could theoretically be administered to patients in the hospital immediately after an acute cardiac event.

"Cardiovascular disease is the leading cause of death for men, women and people of most racial and ethnic groups in the United States," Griffin says. "New and better medicines are needed for those at risk of disease, and cardiac myosin gives us a promising avenue to pursue."
-end-
Authors of the study, "Cardiac Myosin Promotes Thrombin Generation and Coagulation In Vitro and In Vivo," include Jevgenia Zilberman-Rudenko, Hiroshi Deguchi, Meenal Shukla, Yoshimasa Oyama, Jennifer N. Orje, Zihan Guo, Tine Wyseure, Laurent O. Mosnier, Owen J.T. McCarty, Zaverio M. Ruggeri, Tobias Eckle and John H. Griffin.

The work was supported by the American Heart Association and multiple grants from the National Institutes of Health.

Scripps Research is an independent, nonprofit biomedical institute ranked the most influential in the world for its impact on innovation. With campuses in La Jolla, California, and Jupiter, Florida, we are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 U.S. programs for chemistry and biological sciences. Learn more at http://www.scripps.edu.

Scripps Research Institute

Related Heart Attack Articles:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication
Molecular imaging identifies link between heart and kidney inflammation after heart attack
Whole body positron emission tomography (PET) has, for the first time, illustrated the existence of inter-organ communication between the heart and kidneys via the immune system following acute myocardial infarction.
Muscle protein abundant in the heart plays key role in blood clotting during heart attack
A prevalent heart protein known as cardiac myosin, which is released into the body when a person suffers a heart attack, can cause blood to thicken or clot--worsening damage to heart tissue, a new study shows.
New target identified for repairing the heart after heart attack
An immune cell is shown for the first time to be involved in creating the scar that repairs the heart after damage.
Heart cells respond to heart attack and increase the chance of survival
The heart of humans and mice does not completely recover after a heart attack.
A simple method to improve heart-attack repair using stem cell-derived heart muscle cells
The heart cannot regenerate muscle after a heart attack, and this can lead to lethal heart failure.
Mount Sinai discovers placental stem cells that can regenerate heart after heart attack
Study identifies new stem cell type that can significantly improve cardiac function.
Fixing a broken heart: Exploring new ways to heal damage after a heart attack
The days immediately following a heart attack are critical for survivors' longevity and long-term healing of tissue.
Heart patch could limit muscle damage in heart attack aftermath
Guided by computer simulations, an international team of researchers has developed an adhesive patch that can provide support for damaged heart tissue, potentially reducing the stretching of heart muscle that's common after a heart attack.
How the heart sends an SOS signal to bone marrow cells after a heart attack
Exosomes are key to the SOS signal that the heart muscle sends out after a heart attack.
More Heart Attack News and Heart Attack Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Warped Reality
False information on the internet makes it harder and harder to know what's true, and the consequences have been devastating. This hour, TED speakers explore ideas around technology and deception. Guests include law professor Danielle Citron, journalist Andrew Marantz, and computer scientist Joy Buolamwini.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

How to Win Friends and Influence Baboons
Baboon troops. We all know they're hierarchical. There's the big brutish alpha male who rules with a hairy iron fist, and then there's everybody else. Which is what Meg Crofoot thought too, before she used GPS collars to track the movements of a troop of baboons for a whole month. What she and her team learned from this data gave them a whole new understanding of baboon troop dynamics, and, moment to moment, who really has the power.  This episode was reported and produced by Annie McEwen. Support Radiolab by becoming a member today at Radiolab.org/donate.