PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Breakthrough by Temple researchers could lead to new treatment for heart attack

2013-11-06
(Press-News.org) Contact information: Jeremy Walter
Jeremy.Walter@tuhs.temple.edu
215-707-7882
Temple University Health System
Breakthrough by Temple researchers could lead to new treatment for heart attack (Philadelphia, PA) – The stop and start of blood flow to the heart during and after a heart attack causes severe damage to heart cells, reducing their capacity to function and potentially causing their death. But a recent study led by researchers at Temple University School of Medicine suggests that it is possible to limit the extent of that damage using a drug. In experiments in mice that recapitulated a human clinical scenario, they discovered that inhibition of a heart protein called TNNI3K reduced damage from heart attack and protected the heart from further injury.

The findings have significant potential for translation into heart attack patients in a clinical setting. "Many times, what is done in a lab setting can't be done in patients," explained Ronald Vagnozzi, PhD, lead author on the new study, which appeared October 16 in Science Translational Medicine. "But we were interested in a real-world scenario."

Working with senior investigators Thomas L. Force, MD, Professor and Clinical Director at Temple University School of Medicine's (TUSM) Center for Translational Medicine, and Muniswamy Madesh, PhD, Assistant Professor in Temple's Department of Biochemistry, Cardiovascular Research Center, and Center for Translational Medicine, Vagnozzi created a real-world clinical scenario in mice by mimicking blockage of an artery to induce heart attack and then administering a TNNI3K inhibitor. When cardiac function was subsequently improved in treated mice versus untreated controls, Vagnozzi and colleagues realized that a TNNI3K inhibitor could have important clinical benefits for human patients.

"TNNI3K is found only in the heart, which makes it interesting biologically and therapeutically," Vagnozzi said. "Although its function was not well understood, TNNI3K lent itself to being a potential therapeutic target for heart attack."

The researchers found that TNNI3K expression is elevated in patients who are suffering from heart failure, which can develop in the years following heart attack. To explore the significance of that elevation, they engineered mice to overexpress TNNI3K. They also created a second set of engineered mice, in which the protein was deleted. They then measured the animals' response to heart attack.

When overexpressed, Vagnozzi and colleagues found that TNNI3K promoted the injury of heart tissue from ischemia (blockage of blood flow) and reperfusion (restoration of blood flow) during and after a heart attack. TNNI3K overexpression in heart cells encouraged the production of superoxide, a reactive molecule from mitochondria, and activated p38 mitogen-activated protein kinase (MAPK), an enzyme that responds to stress signals in cells. The combined result of those activities was impaired mitochondrial function and heart cell death, which worsened ischemia/reperfusion injury. The opposite occurred in mice in which TNNI3K had been deleted—superoxide production and p38 activation were reduced, and injury to the heart was limited. Reductions in heart dysfunction and fibrosis (hardening of heart tissue) were also observed.

The team next collaborated with the pharmaceutical company GlaxoSmithKline (GSK) to identify compounds that were capable of blocking TNNI3K activity. Treatment of wild-type (nonengineered) mice with the compounds following heart attack produced effects that were similar to those observed in mice with TNNI3K deletion.

The new findings open the way to a large-animal study and the development of a TNNI3K inhibitor that can be used in humans. According to Force, the team is planning to move ahead with a large-animal study, which will determine whether the drugs are effective in animals other than mice and allow for the development of pharmacological and safety profiles of the compounds. "Because TNNI3K is only expressed in the heart, drugs targeting it should be reasonably safe," Force noted.

A major aim of Temple's Center for Translational Medicine is facilitating the delivery of new medicines to patients in the clinic, which could happen for TNNI3K inhibitors, if they are proven safe and effective in the next round of animal studies. According to Vagnozzi, who is now at Cincinnati Children's Hospital Medical Center, the continued collaboratory effort between Temple and GSK will be a key component in moving the drugs into the clinic.

Vagnozzi and colleagues' paper was selected for F1000Prime, in which articles in biology and medical research are chosen and their importance rated by leading scientists and clinicians.

Other researchers contributing to the work include Gregory J. Gatto Jr., Lara S. Kallander, Victoria L. T. Ballard, Brian G. Lawhorn, Patrick Stoy, Joanne Philp, and John J. Lepore with the Heart Failure Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area Unit, GlaxoSmithKline; Nicholas E. Hoffman, Karthik Mallilankaraman, and Erhe Gao at Temple's Center for Translational Medicine; Alan P. Graves with Platform Technology and Sciences, GlaxoSmithKline; and Yoshiro Naito from the Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine in Japan.

INFORMATION:

The research was jointly funded by National Heart, Lung, and Blood Institute grants HL-061688, HL-091799, HL-106380, and HL-086699; an American Heart Association predoctoral fellowship; a Shared Instrumentation Program grant, 1S10RR027327; and the Scarperi family.

About Temple Health

Temple Health refers to the health, education and research activities carried out by the affiliates of Temple University Health System and by Temple University School of Medicine.

Temple University Health System (TUHS) is a $1.4 billion academic health system dedicated to providing access to quality patient care and supporting excellence in medical education and research. The Health System consists of Temple University Hospital (TUH), ranked among the "Best Hospitals" in the region by U.S. News & World Report; TUH-Episcopal Campus; TUH-Northeastern Campus; Fox Chase Cancer Center, an NCI-designated comprehensive cancer center; Jeanes Hospital, a community-based hospital offering medical, surgical and emergency services; Temple Transport Team, a ground and air-ambulance company; and Temple Physicians, Inc., a network of community-based specialty and primary-care physician practices. TUHS is affiliated with Temple University School of Medicine.

Temple University School of Medicine (TUSM), established in 1901, is one of the nation's leading medical schools. Each year, the School of Medicine educates approximately 840 medical students and 140 graduate students. Based on its level of funding from the National Institutes of Health, Temple University School of Medicine is the second-highest ranked medical school in Philadelphia and the third-highest in the Commonwealth of Pennsylvania. According to U.S. News & World Report, TUSM is among the top 10 most applied-to medical schools in the nation.

END



ELSE PRESS RELEASES FROM THIS DATE:

Calculating the risk: Child sexual assault

2013-11-06
Calculating the risk: Child sexual assault Affluent girls residing in two-parent homes are much less likely to be sexually assaulted than other female youth, according to a new study from the University of Iowa. The research revealed that when family income reaches 400 ...

Effects of chronic stress can be traced to your genes

2013-11-06
Effects of chronic stress can be traced to your genes Researchers find similar stress response characteristics in mice and humans COLUMBUS, Ohio – New research shows that chronic stress changes gene activity in immune cells before they reach the bloodstream. With ...

Bringing out the best in X-ray crystallography data

2013-11-06
Bringing out the best in X-ray crystallography data "Function follows form" might have been written to describe proteins, as the M. C. Escher-esque folds and twists of nature's workhorse biomolecules enables each to carry out its specific responsibilities. ...

Pitt Public Health analysis challenges assumptions about bisexual men and HIV transmission

2013-11-06
Pitt Public Health analysis challenges assumptions about bisexual men and HIV transmission BOSTON, Nov. 6, 2013 – The number of HIV positive men who have sex with both men and women is likely no higher than the number of HIV positive ...

Ditty bag of condoms, home-use instructions lead to improved comfort and consistency with condom use

2013-11-06
Ditty bag of condoms, home-use instructions lead to improved comfort and consistency with condom use BOSTON -- A new and successful strategy for combating the spread of sexually transmitted diseases such as HIV draws from an old idea: Practice is fundamental to learning, ...

Conversations between lovers about STIs are important in theory but difficult in bed

2013-11-06
Conversations between lovers about STIs are important in theory but difficult in bed BOSTON -- Having sex can be fun; and talking about sex can be fun. Talking about sexually transmitted infections with a sexual interest, however, is a totally different matter, according to ...

Transgender controversies can lead to 'gender panic,' study finds

2013-11-05
Transgender controversies can lead to 'gender panic,' study finds Transgender controversies can lead to 'gender panic,' study finds When New York City moved in 2006 to make it easier for transgender people to revise the gender on their birth certificates, the proposal ...

Researchers unmask centuries-old elephant imposter

2013-11-05
Researchers unmask centuries-old elephant imposter Through state-of-the-art ancient DNA and protein research and an extensive investigation of historical literature, researchers have determined a 300-year-old type specimen ...

Do you want the good news or the bad news first?

2013-11-05
Do you want the good news or the bad news first? UC Riverside researchers find that where positive information comes in a bad-news conversation can influence outcomes RIVERSIDE, Calif. — There's good news and there's bad news. Which do you want to ...

Positive results for non surgical heart valve replacement

2013-11-05
Positive results for non surgical heart valve replacement MAYWOOD, Il. – Loyola University Medical Center is the only Chicago hospital participating in a landmark clinical trial of an artificial aortic heart valve that does not require open heart surgery. First ...

LAST 30 PRESS RELEASES:

Salk scientist Joseph Ecker awarded McClintock Prize for Plant Genetics and Genome Studies

ADHD: Women are diagnosed five years later than men, despite symptoms appearing at the same age.

Power plants may emit more pollution during government shutdowns

Increasing pressures for conformity de-skilling and demotivating teachers, study warns

Researchers develop smarter menstrual product with potential for wearable health monitoring

Microwaves for energy-efficient chemical reactions

MXene current collectors could reduce size, improve recyclability of Li-ion batteries

Living near toxic sites linked to aggressive breast cancer

New discovery could open door to male birth control

Wirth elected Fellow of American Physical Society

The Journal of Nuclear Medicine Ahead-of-Print Tip Sheet: October 10, 2025

Destined to melt

Attitudes, not income, drive energy savings at home

The playbook for perfect polaritons

‘Disease in a dish’ study of progressive MS finds critical role for unusual type of brain cell

Solar-powered method lights the way to a ‘de-fossilized’ chemical industry

Screen time linked to lower academic achievement among Ontario elementary students

One-year outcomes after traumatic brain injury and early extracranial surgery in the TRACK-TBI Study

Enduring outcomes of COVID-19 work absences on the US labor market

Affirmative action repeal and racial and ethnic diversity in us medical school admissions

Cancer progression illuminated by new multi-omics tool

Screen time and standardized academic achievement tests in elementary school

GLP-1RA order fills and out-of-pocket costs by race, ethnicity, and indication

Study finds HEPA purifiers alone may not be enough to reduce viral exposure in schools

UVA Health developing way to ID people at risk of dangerous lung scarring even before symptoms appear

How can we know when curing cancer causes myocarditis?

Male infertility in Indian men linked to lifestyle choices and hormonal imbalances

An acoustofluidic device for sample preparation and detection of small extracellular vesicles

The advent of nanotechnology has ushered in a transformative era for oncology, offering unprecedented capabilities for targeted drug delivery and controlled release. This paradigm shift enhances thera

A prototype LED as thin as wallpaper — that glows like the sun

[Press-News.org] Breakthrough by Temple researchers could lead to new treatment for heart attack