MedicineWorld.Org
Your gateway to the world of medicine
Home
News
Cancer News
About Us
Cancer
Health Professionals
Patients and public
Contact Us
Disclaimer

Medicineworld.org: Gene Transfer Using Mutant Form Of Good Cholesterol

Back to heart watch blog Blogs list Cancer blog  


Subscribe To Heart Watch Blog RSS Feed  RSS content feed What is RSS feed?

Gene Transfer Using Mutant Form Of Good Cholesterol

Gene Transfer Using Mutant Form Of Good Cholesterol
Transfer of a gene that produces a mutant form of good cholesterol provides significantly better anti-plaque and anti-inflammation benefits than treatment using the "normal" HDL gene, as per a mouse study conducted by cardiology scientists at Cedars-Sinai Medical Center and published in the Oct. 3 issue of the Journal of the American College of Cardiology.

Apolipoprotein A-I is a naturally occurring component of normal HDL (high-density lipoprotein), the "good" cholesterol that circulates in the blood stream. Apolipoprotein A-I Milano is a mutant form, which was originally found in a small number of individuals in Italy who appear to be protected from cholesterol-related heart disease. Scientists are studying the possibility of treating vascular inflammation and plaque buildup through the transfer of protective genes.

"There has been uncertainty and controversy about whether apo A-I Milano is a better form of HDL than the "wild type" (regular) apo A-I in terms of protective effect against atherosclerosis and vascular inflammation, which are tied together," said Prediman K. Shah, M.D., director of the Division of Cardiology and the Atherosclerosis Research Center at Cedars-Sinai.

"We used a unique approach to do a head-to-head comparison, which allowed us to conclusively ascertain the differences between the two genes. Our study demonstrated that A-I Milano gene transfer is much more effective in reducing plaque and vascular inflammation than the normal (wild type) form of apo A-I," said Shah, the article's senior author.

In comparison to control, wild type apo A-I gene transfer led to about a 25 percent decrease in the amount of plaque buildup in the animals' aortas and other vessels. Apo A-I Milano gene transfer resulted in a 65 percent reduction. The amount of gene product (protein) produced by each gene was identical, measured in the blood and in the plaque.

The experiments were conducted in female mice bred to lack the apo A-I gene and the apo E gene. Without these genes, they develop very high cholesterol levels and arterial plaque and are incapable of producing their own apo A-I.

"Any apo A-I that these mice have will come from our gene transfer, making the experimental design very clean," Shah noted.

The genes were transferred to the female mice during a bone marrow transplant from male mice. Because male DNA carries a y chromosome and female DNA does not, the gender mismatch enabled the scientists to precisely track the donor bone marrow.

To deliver the gene to the arterial wall, the scientists used a "signal molecule" when they put the genes into the bone marrow. The signal molecule selectively goes into immune system cells called macrophages, which go into the arterial wall.

"We examined the ability of both the wild type and the apo A-I Milano gene to move cholesterol out of the macrophages, a process called cholesterol efflux. This is one of the mechanisms by which HDL and apo A-I work to reduce plaque: They facilitate the removal of cholesterol from the macrophages in the plaque and deliver it to the liver for elimination," Shah said. "We used three methods in our experiment and all three methods demonstrated that macrophages containing the apo A-I Milano gene were more effective in effluxing cholesterol out of them, in comparison to those carrying the wild type apo A-I gene. Therefore, we concluded, the greater beneficial effect of A-I Milano gene transfer is most likely correlation to a greater efficiency of A-I Milano in promoting the removal of cholesterol from the macrophages".

Shah, who holds the Shapell and Webb Family Endowed Chair in Cardiology at Cedars-Sinai, has been studying apo A-I Milano in its various forms for about 13 years. He and colleagues developed a synthetic version of the protein and conducted animal studies at Cedars-Sinai that led to human trials at the Cleveland Clinic in which intravenous injections were found to shrink plaque in human coronary arteries.

The Cedars-Sinai researchers, collaborating with scientists from Sweden, also are in the process of developing vaccine against LDL cholesterol (bad cholesterol) that one day may be administered in childhood to provide lifelong protection against vascular inflammation and plaque.

The gene treatment research was supported by grants from the National Institutes of Health, the Eisner Foundation, Entertainment Industry Foundation, Milken Family Foundation, United Hostesses and The Heart Foundation.


Posted by: Daniel    Source




Did you know?
Transfer of a gene that produces a mutant form of good cholesterol provides significantly better anti-plaque and anti-inflammation benefits than treatment using the "normal" HDL gene, as per a mouse study conducted by cardiology scientists at Cedars-Sinai Medical Center and published in the Oct. 3 issue of the Journal of the American College of Cardiology.

Medicineworld.org: Gene Transfer Using Mutant Form Of Good Cholesterol

Main Page| Cancer blog| Cancer blogs list| Lung cancer blog| Colon cancer blog| Prostate cancer blog| Breast cancer blog| Diabetes watch blog| Heart watch blog| Allergy blog| Bladder cancer blog| Cervical cancer blog| Colon cancer news blog| Diabetes news blog| Esophageal cancer blog| Gastric cancer blog| Health news blog| Heart news blog| Infectious disease blog| Kidney watch blog| Lung disease blog| Lung cancer news blog| Mesothelioma blog| Neurology blog| Breast cancer news blog| OBGYN blog| Ophthalmology blog| Ovarian cancer blog| Cancer news blog| Pancreas cancer blog| Pediatrics blog| Prostate cancer news blog| Psychology blog| Research blog| Rheumatology blog| Society news blog| Uterine cancer blog| Weight watch blog|

Copyright statement
The contents of this web page are protected. Legal action may follow for reproduction of materials without permission.