Nav: Home

Oklahoma researchers find that a biological 'good guy' has a dark side

May 04, 2016

A pair of Oklahoma Medical Research Foundation scientists have discovered that an enzyme previously thought only to be beneficial could, in fact, pose significant danger to developing embryos. The new research could have implications not only for prenatal development but also for treating lymphedema and liver damage resulting from acetaminophen overdose.

Using genetically engineered mouse embryos, OMRF's Courtney Griffin, Ph.D., and Patrick Crosswhite, Ph.D., looked at what would happen if they removed a protein that determines how genes get turned on and off during blood vessel development.

The scientists found a marked increase in the activity of plasmin, an enzyme that is known to help break up blood clots and promote blood vessel development. But in a developing embryo, said Griffin, too much of the enzyme can pose a threat.

"Plasmin has always been seen in a positive light, but we're not finding any beneficial aspects of it in early development," said Griffin. "In fact, excessive plasmin does dangerous things in a growing embryo."

The OMRF researchers also found that liver damage could ensue in embryos when the protein that suppresses plasmin activity--known as CHD4--was absent. Too much plasmin makes liver blood vessels fragile and prone to bleeding. They also found that excess plasmin could be harmful to the lymph system, an essential part of the immune system, by breaking down blood clots that help the lymphatic system function properly.

With this new information, Griffin and Crosswhite will study plasmin behavior later in gestation and in adults. They'll investigate how high concentration of plasmin may contribute to conditions such as lymphedema, a painful lymph disorder marked by swelling in the arms and legs. They'll also look at whether CHD4 continues protecting liver blood vessels from plasmin damage after birth.

More research is needed, said Griffin, but the findings may lead to clinical use of plasmin-blocking compounds after acetaminophen overdose. Acetaminophen is the active ingredient in Tylenol, and overdose is a leading cause of liver damage in the U.S., resulting in up to 70,000 hospitalizations a year. "Excessive plasmin activity in the liver has been linked to acetaminophen overdose," said Crosswhite, "and we suspect this plasmin may make liver blood vessels dangerously weak."

"This work is innovative and creative, from the results to the interpretation and conclusions," said Rodger McEver, M.D., chair of OMRF's Cardiovascular Biology Research Program. "These scientists were able to show that plasmin is really important in ways that hadn't been discovered before. It gives us new information and is great basic science, but the data could be clinically relevant to treating acetaminophen toxicity in humans."

The new findings appear in the May 3 issue of the Journal of Clinical Investigation.
Other OMRF contributors to the paper include Sathish Srinivasan, Ph.D., Lijun Xia, M.D., Ph.D., and Siqi Gao, as well as former OMRF employees Carol Curtis, Ph.D., and Joanna Podsiadlowska.

Funding for the research was made possible by grant number HL111178, HD083418 and HL085607 from the National Institutes of Health and grant number 15POST21180005 from the American Heart Association.

High-resolution photos of Courtney Griffin, Ph.D., and Patrick Crosswhite, Ph.D., are available for download here:

About OMRF

OMRF ( is an independent, nonprofit biomedical research institute dedicated to understanding and developing more effective treatments for human diseases. Its scientists focus on such critical research areas as cancer, diseases of aging, lupus and cardiovascular disease.

Oklahoma Medical Research Foundation

Related Blood Clots Articles:

New ultrasound 'drill' targets deep vein blood clots
Researchers have developed a new surgical tool that uses low-frequency intravascular ultrasound to break down blood clots that cause deep vein thrombosis.
New blood thinner better at preventing recurrent blood clots than aspirin
An international research team with prominent Canadian leadership has found that the blood thinner rivaroxaban is as safe as aspirin, and more effective at preventing recurrence of life-threatening blood clots in the legs and lungs, according to a study being published in the New England Journal of Medicine and presented at the American College of Cardiology's 66th Annual Scientific Session.
Preventing blood clots with a new metric for heart function
Scientists from Johns Hopkins University and Ohio State University have discovered a new method for predicting those most at risk for thrombus, or blood clots, in the heart.
Statins could halt vein blood clots, research suggests
Statins could hold the key to eradicating one of the most preventable causes of hospital deaths after researchers uncovered a new role for the cholesterol-lowering pill.
Exploring why an anticoagulant might create blood clots
An oral anticoagulant drug given to some heart disease patients may actually enhance blood clot formation, according to a new study.
Increased risk of blood clots soon after starting testosterone treatment
Starting testosterone treatment is associated with an increased risk of serious blood clots (known as venous thromboembolism or VTE) that peaks within six months and declines gradually thereafter, concludes a study in The BMJ today.
New technology detects blood clots with simple in-home test
NSF-Funded UC research leads to a screening test for patients on blood thinners to reduce the risk for a blood clot or stroke that's as easy as an in-home diabetes test.
Link found between obesity and blood clots in pediatric patients
Researchers at Wake Forest Baptist Medical Center have found an association between obesity and the formation of blood clots in the veins of children and adolescents.
Detecting when and why deadly blood clots form
Scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University have devised a better assay for testing blood's clotting tendency, also known as hemostasis, which could one day prove lifesaving in a variety of clinical situations in which a patient's health is jeopardized by abnormal blood coagulation and platelet function.
Blood clots may complicate aortic valve replacements
Heart valve replacements made from tissue (bioprosthetic valves) have long been thought to be spared the complication of blood clot formation.

Related Blood Clots Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".