In Milan (or as the Italians say, Milano) Italy some people have a mutation of high density lipoprotein (HDL) cholesterol called Apolipoprotein A-I Milano which is suspected of reducing the risk of heart and cardiovascular disease. In order to investigate whether Apo A-I Milano really does reduce risk of cardiovascular diseases researchers at Cedars-Sinai put human variations of HDL choelsterol into mice and then measured the resulting mice. While normal human HDL cholesterol reduced plaque build-up by 25% the Apo A-I Milano version of the gene reduces plaque build-up by 65%.
LOS ANGELES - Transfer of a gene that produces a mutant form of good cholesterol provides significantly better anti-plaque and anti-inflammation benefits than therapy using the "normal" HDL gene, according to a mouse study conducted by cardiology researchers at Cedars-Sinai Medical Center and reported 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. Researchers 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.
Compared 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.
A gene therapy that converted our livers to make Apo A-I Milano HDL cholesterol would likely reduce both inflammation and the rate of accumulation of damage from oxidation and plaque build-up in the circulatory system. My guess is such a treatment would reduce the amount of free radicals in the blood and therefore also reduce the rate of brain aging.
Drugs that raise the concentration of HDL cholesterol will hit the market many years before a gene therapy that converts our bodies to make Apo A-I Milano HDL. We might also see clinical use of intravenous administration of Apo A-I Milano HDL as a way to get a bigger and quicker benefit, especially for those suffering angina. Also see my post Synthetic HDL Cholesterol Reduces Artery Clogging In 6 Weeks.
|Share |||Randall Parker, 2006 September 28 11:23 PM Biotech Cardiovascular|