By Paul E. Ramey
GAINESVILLE, Fla.---Gene therapy in laboratory animals successfully prevents high blood pressure and its damaging effects on the heart and kidneys, report researchers at the University of Florida and University of Alabama.
Previous UF research has demonstrated that high blood pressure, or hypertension, can be prevented in laboratory animals, but UF researchers Mohan Raizada, Craig H. Gelband, and Michael Katovich, of the departments of physiology and pharmacodynamics, believe this is the first animal study to show the heart and kidneys also can be protected. One day, scientists hope gene therapy will be able to control high blood pressure in humans.
The researchers describe their findings in the March 3 issue of the journal "Proceedings of the National Academy of Sciences."
In the latest study, one of several funded by the National Institutes of Health, researchers used an altered form of DNA in rats to decrease the effectiveness of angiotensin II, a naturally occurring hormone that plays a role in regulating blood pressure. DNA is the spiral-shaped genetic material contained in every living cell that transmits all hereditary characteristics. Scientists generally believe genetics may play a role in hypertension, although the exact cause of most cases is unknown.
"Hypertension affects so many people, and this study is one small piece of the puzzle that we hope will aid our efforts to find a cure," said Raizada, a professor of physiology and associate dean of graduate education in UF's College of Medicine.
"We've shown that through gene therapy we can prevent hypertension and damage to the target organs up to at least 120 days in rats. While this particular study would not be performed in a clinical setting, 120 days is the equivalent of 15 to 20 years in a human," he said.
High blood pressure kills about 40,000 people each year in the United States and contributes to the deaths of 200,000 others. The American Heart Association estimates as many as 50 million Americans 6 and older have high blood pressure, and 35 percent of them do not know it.
High blood pressure is particularly prevalent in blacks, heavy drinkers, women taking oral contraceptives, and those who are middle-aged, elderly or obese.
Though high blood pressure is easily detected and usually controllable with daily medication, doctors are unsure whether this treatment reverses other hypertension-induced changes in the body, such as heart and kidney damage.
In the UF study, researchers treated rats genetically predisposed to high blood pressure with antisense, a form of DNA in which the normal genetic code is reversed. The antisense is packaged within an inactivated, harmless virus called a retrovirus and injected into the bloodstream. The antisense interacts with the cell wall to reduce the potentially harmful effects of the angiotensin II hormone. High blood pressure and organ damage were prevented in all of the animals in which the treatment was successfully delivered.
"There are a number of pathophysiological changes associated with high blood pressure and we chose to look at six," said Gelband, an assistant professor of physiology in the UF College of Medicine. "All six of these problems were prevented. We now plan to study whether gene therapy can reverse organ damage in adult animals with high blood pressure."
Gene therapy studies for high blood pressure have been under way at UF for a number of years. M. Ian Phillips, professor and College of Medicine physiology department chairman, previously has shown gene therapy can reduce high blood pressure in adult animals.
Jeffrey Martens, a graduate student in pharmacology and the current paper's lead author, said gene therapy may someday offer an alternative treatment for people genetically predisposed to high blood pressure.
"We have not identified the gene that causes high blood pressure, and are not completely sure the disease is genetic. There could be other factors involved, including diet and lifestyle," he said.
Other collaborators on the study include Phyllis Reaves, a postdoctoral fellow in physiology; Dr. Di Lu, a resident in pathology; and Kathleen Berecek and Sanford Bishop of the University of Alabama, Birmingham.
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