(Press-News.org) NEW YORK (Jan. 4, 2013) -- A cocktail of three specific genes can reprogram cells in the scars caused by heart attacks into functioning muscle cells, and the addition of a gene that stimulates the growth of blood vessels enhances that effect, said researchers from Weill Cornell Medical College, Baylor College of Medicine and Stony Brook University Medical Center in a report that appears online in the Journal of the American Heart Association.
"The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting," said Dr. Todd K. Rosengart, chair of the Michael E. DeBakey Department of Surgery at BCM and the report's corresponding author. "The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle. However, in these animal studies, we found that even the effect is enhanced when combined with the VEGF gene."
"This experiment is a proof of principle," said Dr. Ronald G. Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College and a pioneer in gene therapy, who played an important role in the research. "Now we need to go further to understand the activity of these genes and determine if they are effective in even larger hearts."
During a heart attack, blood supply is cut off to the heart, resulting in the death of heart muscle. The damage leaves behind a scar and a much weakened heart. Eventually, most people who have had serious heart attacks will develop heart failure.
Changing the scar into heart muscle would strengthen the heart. To accomplish this, during surgery, Rosengart and his colleagues transferred three forms of the vascular endothelial growth factor (VEGF) gene that enhances blood vessel growth or an inactive material (both attached to a gene vector) into the hearts of rats. Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material. (A transcription factor binds to specific DNA sequences and starts the process that translates the genetic information into a protein.)
The GMT genes alone reduced the amount of scar tissue by half compared to animals that did not receive the genes, and there were more heart muscle cells in the animals that were treated with GMT. The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes. (Ejection fraction refers to the percentage of blood that is pumped out of a filled ventricle or pumping chamber of the heart.)
The hearts of the animals that had received both the GMT and the VEGF gene transfers had an ejection fraction four times greater than that of the animals that had received only the GMT transfer.
Rosengart emphasizes that more work needs to be completed to show that the effect of the VEGF is real, but it has real promise as part of a new treatment for heart attack that would minimize heart damage.
"We have shown both that GMT can effect change that enhances the activity of the heart and that the VEGF gene is effective in improving heart function even more," said Dr. Crystal.
The idea started with the notion of induced pluripotent stem cells – reprograming mature specialized cells into stem cells that are immature and can differentiate into different specific cells needed in the body. Dr. Shinya Yamanaka and Sir John B. Gurdon received the Nobel Prize in Medicine and Physiology for their work toward this goal this year.
However, use of induced pluripotent stem cells has the potential to cause tumors. To get around that, researchers in Dallas and San Francisco used the GMT cocktail to reprogram the scar cells into cardiomyocytes (cells that become heart muscle) in the living animals.
Now Rosengart and his colleagues have gone a step farther – encouraging the production of new blood vessels to provide circulation to the new cells.
INFORMATION:
Others who took part in this work include Megumi Mathison, Ronald Gersch, Ahmed Nasser, Sarit Lilo, Mallory Korman, Mitchell Fourman, Kenneth Shroyer, Jianchang Yang, Yupo Ma, all of Stony Brook University Medical Center and Neil Hackett of Weill Cornell Medical College.
Funding for this work came from the generosity of James and Lisa Cohen.
Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.
END
TAMPA, Fla. (Jan. 4, 2013) – Researchers from the University of South Florida and colleagues at the James A. Haley Veterans' Hospital studying the long-term consequences of traumatic brain injury (TBI) using rat models, have found that, overtime, TBI results in progressive brain deterioration characterized by elevated inflammation and suppressed cell regeneration. However, therapeutic intervention, even in the chronic stage of TBI, may still help prevent cell death.
Their study is published in the current issue of the journal PLOS ONE.
"In the U.S., an estimated 1.7 ...
Pennsylvania Court Denies Disability Benefits in Misconduct Case
A Pennsylvania court ruled recently that a worker who had been injured on the job was not entitled to receive total disability benefits after she was later terminated for alcohol-related misconduct. The court's decision in BJ Wholesale Club v. Workers' Compensation Appeal Board could affect the ability of other injured Pennsylvania workers to receive workers' compensation benefits when they are terminated for misconduct unrelated to an injury that would otherwise entitle them to benefits.
Workers' Compensation ...
The Importance of Parenting Plans
When a couple is splitting up, emotions run high and it is easy to get wrapped up in the heat of the moment. But when it comes to what is best for a child, cooler heads should always prevail. In order to ensure that their children's needs always take precedence over parents' emotions, many divorced parents create parenting plans that outline their child custody rights and responsibilities.
What Should Be Included in a Parenting Plan?
-Custody issues: One of the most important aspects of a parenting plan is outlining who will get ...
Creation of Postnuptial Agreements on the Rise
While prenuptial agreements are fairly common, many people are not aware that they may be able to create a postnuptial agreement, which can include a lot of the same information that you would find in a prenuptial agreement, but it is done after the couple has gotten married. In fact, according to the American Academy of Matrimonial Lawyers, from 2002 to 2007, attorneys reported a dramatic increase in the number of postnuptial agreements drafted for their clients.
In many cases, couples will have a postnuptial agreement ...
Rebuilding Credit: Getting a Mortgage after Bankruptcy
Bankruptcy is a way for struggling borrowers to get a fresh start. Qualifying borrowers can have debt forgiven (discharged), reduced or consolidated into affordable payments. Despite the negative impact a bankruptcy can have on a credit score, there are things that can be done to assist with purchasing a home and getting a mortgage after a bankruptcy.
Most borrowers find that they may be eligible to apply for a mortgage within one to four years depending on the type of bankruptcy that is filed. FHA or VA loans ...
California beginning to bounce back from housing crisis
For those facing foreclosure in California there is hope. According to RealtyTrac, California has some of the highest rates of foreclosure in the country, but cities in the state are seeing substantial declines in the number of foreclosures. The California legislature changed the laws in July and provided more protections for struggling homeowners.
California hit hard by housing crisis
California was hit hard by the foreclosure crisis and the state is still struggling with very high rates even though the rates ...
How Social Security Disability's compassionate allowances work
Over the last few years, the Social Security Administration has taken steps to fast-track the application process for Social Security Disability Insurance for individuals whose conditions are obviously disabling. The decision to fast-track an application is known as a compassionate allowance and can provide disability benefits more quickly to those who are clearly in need.
Compassionate allowances provided for those with certain conditions
To be eligible for a compassionate allowance, applicants must ...
Social Security benefits may improve life after disability
Social Security Disability Insurance, or SSDI, can provide additional income to those permanently disabled and no longer able to work and who are receiving workers' compensation, private insurance or other disability benefits. In fact, SSDI benefits have numerous advantages over other disability benefits and can be a good addition to a disabled worker's financial support.
SSDI may extend health care coverage
One of the most important benefits SSDI may provide is an extension of COBRA health care insurance ...
New Bill in Utah May Change How Alimony Is Calculated
Divorce is a complicated legal process that deals with a wide range of issues. Depending on the couple, a divorce proceeding may need to address child custody, whether alimony should be distributed and how to divide property.
Each of these issues is fairly complex on its own, and the laws surrounding them are often changing. In fact, another change may be on the horizon. Currently, legislators in Utah are taking a second look at how the state handles the issue of alimony determinations in divorce.
Sen. Lyle ...
Pedestrian Traffic Fatalities on the Rise
Walking and biking are excellent transportation methods. Traveling as a pedestrian is healthy, inexpensive and uses up fewer global resources than driving. Perhaps that is why pedestrian travel has risen in public awareness in recent years, and why communities across the U.S. are attempting to increase the accessibility of bike and walking areas for the public.
With the increasing number of pedestrians on the road comes an increasing need for pedestrian safety. Overall traffic deaths are down from previous years, with the ...
