Navigate Up
UPMC/University of Pittsburgh Schools of the Health Sciences
Patients and medical professionals may call 1-800-533-UPMC (8762) for more information.

University Of Pittsburgh Researchers Use Gene Therapy To Prevent Cardiac Rupture And Prolong Life In Mouse Model Of Heart Attack

DALLAS, November 16, 2005 — A University of Pittsburgh research team has found that gene vector carrying an inhibitor of metalloproteinase-2 (MMP-2), a protein shown to stimulate adverse healing in heart tissue after a heart attack, protected experimental mice against further cardiac damage and subsequent death.

Furthermore, the benefits correlated with a partial restoration of the normal ratios between metalloproteinase-2 and its specific inhibitor, known as tissue inhibitor of metalloproteinase-2 (TIMP-2). These results are being reported at the annual meeting of the American Heart Association, Nov. 13-16 in Dallas. Further studies are needed to determine the mechanism of this protective effect.

“Induction of metalloproteinases has been shown to contribute to adverse remodeling of cardiac tissue after myocardial infarction," according to Charles McTiernan, Ph.D., research assistant professor in the division of cardiology at the University of Pittsburgh School of Medicine . “It has been hypothesized that supplementing post-MI tissue with TIMP-2 can normalize the balance of metalloproteinases and their specific inhibitors and protect against the damage of myocardial infarction.”

To determine if gene therapy could be used to improve outcomes following a heart attack, Dr. McTiernan and his coworkers gave one group of mice with experimental myocardial infarctions (MI) an injection of viral particles containing the TIMP-2 gene and compared their outcomes to untreated MI and control mice. The investigators then assessed the left ventricular size and function of the surviving mice seven days after their myocardial infarction and also measured MMP-2 and -9 and TIMP-1 and -2 protein levels.

Among the mice that died, the major cause of death was rupturing of cardiac tissue. Among the mice that survived, left ventricular systolic function was not different between the treated and untreated MI mice. However, levels of MMP-2 and - 9 were highest in the untreated MI group. TIMP-1 levels were higher in all MI hearts compared to controls, but there was no significant difference between the treated and untreated MI groups. TIMP-2 levels, however, were highest in the treated MI group. Overall, 34 mice survived till the end of the study period, and survival was significantly better in the TIMP-2-treated group compared with the untreated MI group (56 percent vs. 34 percent respectively, p< 0.02).

©  UPMC | Affiliated with the University of Pittsburgh Schools of the Health Sciences
Supplemental content provided by A.D.A.M. Health Solutions. All rights reserved.

For help in finding a doctor or health service that suits your needs, call the UPMC Referral Service at 412-647-UPMC (8762) or 1-800-533-UPMC (8762). Select option 1.

UPMC is an equal opportunity employer. UPMC policy prohibits discrimination or harassment on the basis of race, color, religion, ancestry, national origin, age, sex, genetics, sexual orientation, marital status, familial status, disability, veteran status, or any other legally protected group status. Further, UPMC will continue to support and promote equal employment opportunity, human dignity, and racial, ethnic, and cultural diversity. This policy applies to admissions, employment, and access to and treatment in UPMC programs and activities. This commitment is made by UPMC in accordance with federal, state, and/or local laws and regulations.

Medical information made available on UPMC.com is not intended to be used as a substitute for professional medical advice, diagnosis, or treatment. You should not rely entirely on this information for your health care needs. Ask your own doctor or health care provider any specific medical questions that you have. Further, UPMC.com is not a tool to be used in the case of an emergency. If an emergency arises, you should seek appropriate emergency medical services.

For UPMC Mercy Patients: As a Catholic hospital, UPMC Mercy abides by the Ethical and Religious Directives for Catholic Health Care Services, as determined by the United States Conference of Catholic Bishops. As such, UPMC Mercy neither endorses nor provides medical practices and/or procedures that contradict the moral teachings of the Roman Catholic Church.

© UPMC
Pittsburgh, PA, USA UPMC.com