GAINESVILLE, Fla.—University of Florida researchers have identified a drug compound that may prevent tissue damage associated with cardiovascular disease, according to a study published in the May 1 edition of the American Heart Association journal Hypertension.
Using a rational, structure-based approach, the researchers found a compound that enhances the activity of angiotensin-converting enzyme II (ACE2), an enzyme that helps protect the cardiovascular system. The compound dramatically lowered blood pressure, improved heart function and prevented damage to the heart and kidneys of rats with hypertension.
Study author Dr. David Ostrov, an assistant professor in the University of Florida College of Medicine's Department of Pathology, Immunology and Laboratory Medicine, says the finding could lead to a new class of antihypertensive drugs designed to control heart disease.
"I expect that the drug discovery industry will be particularly interested in building on this study in two ways," Ostrov says. "First, the structure-based method to identify compounds that enhance activity will likely be a useful strategy for a large number of target proteins where the therapeutic goal is to enhance function. Second, the drug discovery industry may focus efforts in defining a novel series of FDA-approved drugs in this new class of anti-hypertensive agents: ACE-2 activators."
ACE produces angiotensin II, a potent hormone that causes high blood pressure. ACE2 works in harmony with ACE, but lowers levels of angiotensin II and generates peptides that dilate blood vessels. The researchers hypothesized that enhancing the activity of ACE2 could be beneficial, but knew this was contrary to the accepted approach of inhibiting ACE activity.
Researchers used a "supercomputer" to process 140,000 prospective drug compounds. The researchers then selected the top 10 scoring compounds, tested them in biochemical assays and found two compounds that enhanced ACE2 activity. After hitting on the lead compound, researchers then tested it in hypertensive rats. Tissue samples from the rats revealed a significant decrease in fibrosis of the heart, kidney and blood vessels.
Ostrov says the study, funded by grants from the NIH and the American Heart Association, also showed the compound inhibits inflammation, which has significant implications for many other human diseases. Additional research will continue to explore the compound's effectiveness in animals and humans.
"These findings will be used in the near future by a number of labs to extend the observations for the ACE2 specific compounds in other animal models for human diseases, (such as) pulmonary hypertension, Type I diabetes, systemic lupus erythematosus, Alzheimer's Disease and cancer," Ostrov says. DDN
Using a rational, structure-based approach, the researchers found a compound that enhances the activity of angiotensin-converting enzyme II (ACE2), an enzyme that helps protect the cardiovascular system. The compound dramatically lowered blood pressure, improved heart function and prevented damage to the heart and kidneys of rats with hypertension.
Study author Dr. David Ostrov, an assistant professor in the University of Florida College of Medicine's Department of Pathology, Immunology and Laboratory Medicine, says the finding could lead to a new class of antihypertensive drugs designed to control heart disease.
"I expect that the drug discovery industry will be particularly interested in building on this study in two ways," Ostrov says. "First, the structure-based method to identify compounds that enhance activity will likely be a useful strategy for a large number of target proteins where the therapeutic goal is to enhance function. Second, the drug discovery industry may focus efforts in defining a novel series of FDA-approved drugs in this new class of anti-hypertensive agents: ACE-2 activators."
ACE produces angiotensin II, a potent hormone that causes high blood pressure. ACE2 works in harmony with ACE, but lowers levels of angiotensin II and generates peptides that dilate blood vessels. The researchers hypothesized that enhancing the activity of ACE2 could be beneficial, but knew this was contrary to the accepted approach of inhibiting ACE activity.
Researchers used a "supercomputer" to process 140,000 prospective drug compounds. The researchers then selected the top 10 scoring compounds, tested them in biochemical assays and found two compounds that enhanced ACE2 activity. After hitting on the lead compound, researchers then tested it in hypertensive rats. Tissue samples from the rats revealed a significant decrease in fibrosis of the heart, kidney and blood vessels.
Ostrov says the study, funded by grants from the NIH and the American Heart Association, also showed the compound inhibits inflammation, which has significant implications for many other human diseases. Additional research will continue to explore the compound's effectiveness in animals and humans.
"These findings will be used in the near future by a number of labs to extend the observations for the ACE2 specific compounds in other animal models for human diseases, (such as) pulmonary hypertension, Type I diabetes, systemic lupus erythematosus, Alzheimer's Disease and cancer," Ostrov says. DDN
