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For Immediate Release

 

Story contact:

Mark Stayton: (307) 766-4025

stayton@uwyo.edu

 

 

Contact: Steven L. Miller, Senior Editor

Phone: (307) 766-6342

E-mail: slmiller@uwyo.edu

Archived News Site www.uwyo.edu/agadmin/news/news.htm

 

Date: April 19, 2007

 

 

UW research examines aftereffects of heart attacks in mice

 

            Jacque Keele’s research gets to the heart of the matter.

            The University of Wyoming College of Agriculture doctorate student, under the tutelage of Associate Professor Mark Stayton in the Department of Molecular Biology, is beginning to get data back in her fourth year of research studying what happens to mouse hearts following induced heart attacks.

            Keele, of Loveland, Colo., has confirmed the induction of a certain biochemical pathway, discovered the specific cell type in which the pathway is induced and determined the intracellular location for this pathway.

            Along the way, she just might have gained a little insight into the heart disease both her grandfathers suffer from. “I find it fascinating,” said Keele. 

            Animal studies such as this may suggest new therapies for heart attacks in human patients, said Stayton.  “We are beginning a study in which we artificially down-regulate this biochemical pathway in mice and then look for improved recovery from a heart attack,” he said. 

            Healing and adaptation by the heart takes weeks, said Stayton, “but the ‘on’ switch for recovery is thrown for the recovery process in the first two days.”  Keeler is studying what happens when that switch is thrown.

            During a heart attack, a segment of the heart is deprived of oxygen; the heart begins to enlarge and, with the wedge-shaped dead portion, doesn’t pump as efficiently.

            The team has had the advantage on this of working with Paul Thomas, associate dean and professor in the UW Department of Kinesiology and Health. “His contribution is open heart surgery on mice,” said Stayton.

            Thomas was part of two COBRE (Centers of Biomedical Research Excellence) grants the university received from the National Institutes of Health. Also involved were Stayton, UW faculty members Professor Rich McCormick (Department of Animal Science), Associate Professor Mark Gomelsky (Department of Molecular Biology), and Professor Bill Flynn (Department of Zoology and Physiology), who directed the COBRE.

            “We were all part of the cardiovascular COBRE grant that used myocardial infarction as the experiment model,” Thomas said. “I was the guy creating all the infarctions, probably several thousand in total over the five-year period.”

            Keele’s dissertation research is a spin-off from findings from the COBRE grant that researchers wanted to pursue. “Rich (McCormick) and I have collaborated for 18 years here at UW looking at collagen characteristics in hearts following a variety of interventions/models including myocardial infarction,” said Thomas, also an adjunct professor to the Department of Animal Science.

             A heart attack is induced in a mouse by tying off an artery. Thomas said the surgery takes about 35 minutes. Since the mouse heart is only about 6 millimeters across, a microscope is required for the surgery. “The nice thing is we don’t have to cut any of the superficial chest muscle to get into the chest,” noted Thomas. “We do have to go through the intercostal muscles between the ribs, which creates a pneumothorax (air in a pleural cavity surrounding the lungs).

            A pneumothorax occurs when thoratic air pressure is equalized with the atmosphere.  “Thus, when the ribs expand, the animal is unable to draw air into its lungs and can’t breathe,” said Stayton. “As a result, the animals must be artificially ventilated during surgery.”

            Thomas ties off the left anterior descending coronary (about 200 microns thick) by passing a suture underneath it. A mouse heart beats almost 400 times a minute, requiring a deft touch by Thomas, noted Keele.  The portion of the mouse heart fed by the tied-off artery turns white almost immediately due to the lack of blood, she said. The heart is later removed, and Keele studies the recovery process.

            “We try to understand, in a global sense, all the changes that happen after a heart attack occurs,” said Stayton. “The idea is to make sure people didn’t miss anything when studying heart disease.  Thus, in our initial study, we measured the expression of 37,000 mouse genes at each of six time points after the heart attack and in three distinct regions of the left ventricle using GeneChipsä (a collection of microscopic DNA spots, commonly representing single genes, arrayed on a solid surface by covalent attachment to chemically suitable matrices).”

            When the team analyzed this data, it discovered a biochemical pathway that was upregulated after a heart attack and had not been previously reported. 

            This pathway reduces contractility and may reduce arterial blood flow to the heart, which is not the best for the patient, Stayton said. Drugs like nitroglycerin dilate arteries and increase blood flow to the heart, thus assisting the heart and lessening pain.  This study was published in Mammalian Genome in 2006.

            Keele has identified the heart cell type where the newly discovered pathway is expressed and has determined the intracellular location.  She harvests the infracted mouse heart, about as big as the tip of one’s little finger, freezes the heart, cuts 5-micron-wide slices and then stains to reveal certain proteins.       

            She makes about 50 to 80 slides of a heart. She has studied 24- and 48-hour heart attacks in mice.

            Results of her work will be submitted for publication within the next few weeks.   “I’m very interested in her research as it relates to heart and heart function, which is my principal research interest, and I’m on her dissertation committee,” said Thomas.

            Keele, who plans to find a post-doctorate position, said she loves the work. “Every day it’s something new,” she noted. The research work forced her to be more meticulous, to be more careful in the laboratory and to be more organized.

            Stayton is happy with her performance. “One of the best things about my job is training students,” he said. “People leave here different than when they come in. The same thing happened to me while in training. It’s very demanding. Precision, focus, hard work – all have to come together. Publication comes at the end. It takes awhile for all these things to come together. I’m delighted with her work.”

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