HPCwire: Supercomputer Points Researchers to New Blood Pressure Drug

The Leading Source for Global News and Information Covering the Ecosystem of High Productivity Computing

Leading HPC
Solution Providers

HPCwire >> Industry >> Life Sciences

May 01, 2008

Supercomputer Points Researchers to New Blood Pressure Drug

GAINESVILLE, Fla., May 1 -- University of Florida researchers have identified a drug compound that dramatically lowers blood pressure, improves heart function and -- in a remarkable finding -- prevents damage to the heart and kidneys in rats with persistent hypertension.

The findings, which appear in today’s (May 1) edition of the American Heart Association journal Hypertension, could lead to a new class of antihypertensive drugs designed to address two major problems associated with cardiovascular disease: high blood pressure and the tissue damage associated with it, known as fibrosis.

“When people have heart attacks (or suffer from hypertension) the blood vessels get more rigid,” said study author David Ostrov, an assistant professor in the UF College of Medicine’s department of pathology, immunology and laboratory medicine. “We discovered a compound that reverses the fibrosis that makes the blood vessels more rigid.”

The American Heart Association estimates that 72 million people in the United States have high blood pressure, a major risk factor for stroke, heart attack and death.

Angiotensin-converting enzyme plays a key role in the development of high blood pressure. It produces angiotensin II, a potent hormone that triggers the condition and contributes to the development of cardiovascular disease by constricting blood vessels, causing blood pressure to rise. That’s why millions of Americans with hypertension and cardiovascular disease take ACE inhibitors. But these drugs have limited capacity to repair heart function and to reverse tissue damage.

In contrast, the enzyme ACE2 not only lowers levels of angiotensin II but also converts it to a hormone that helps protect the cardiovascular system.

“Only recently has it come to be appreciated that ACE and ACE2 play a very important role in balancing the activity of the other one to maintain normal blood pressure,” Ostrov said. “They work in harmony.”

Hypothesizing that activating ACE2 could be beneficial, UF scientists set out to discover a compound that enhances the enzyme’s activity.

Researchers used one of the world’s most powerful supercomputers to process 140,000 prospective drug compounds in a matter of weeks. The computer predicted which molecules would be most likely to enhance the activity of ACE2, rotating them in thousands of different orientations to see how they would bind to certain pockets on the enzyme’s surface.

“This project had a very small likelihood of succeeding because it’s much easier to inhibit activity rather than to enhance it. By analogy, it’s easier to break something than to build it,” Ostrov said. “If you consider the structure of an enzyme’s active site it’s easy to see that if you plug up the active site it’s not going to work. But how can one make the enzyme actually work better? This seemed to be a very significant challenge we were probably not likely to overcome. We tried anyway.”

And it worked.

“That in itself is a significant accomplishment because no one has ever specifically identified a compound that enhances the activity of an enzyme using a rational structure-based approach,” he said. “In other words, no one has ever done this before on purpose. People have discovered molecules that enhance the activity of enzymes by trial and error, but no group has ever done it in a specifically pointed way like this.”

Ostrov said the enzyme exists in two forms: like a Pac-Man with a mouth that has chomped closed, and like a Pac-Man with a mouth that remains wide open. The molecule that worked best fit in a structural pocket in the enzyme’s open conformation.

“So in other words, stabilizing the open conformation may be the reason why we enhance the activity of the enzyme,” he said

After hitting on the “lead” compound, UF researchers then tested it in hypertensive rats that had developed fibrosis of the heart and kidney. The animals received the drug for two weeks. Tissue samples from treated animals revealed a significant decrease in fibrosis of the heart, kidney and blood vessels, said Ostrov, who described the findings as “striking and reproducible.”

The study was funded by grants from the National Institutes of Health and the American Heart Association and was a collaborative effort of the UF colleges of Medicine, Pharmacy and Liberal Arts and Sciences. Researchers also included Mohan Raizada, a distinguished professor of physiology and functional genomics, Michael J. Katovich, a professor of pharmacodynamics, and Ronald K. Castellano, an assistant professor of chemistry, among others.

Early results also show the compound inhibits inflammation, which has significant implications for a number of human diseases, including autoimmune diseases such as type 1 diabetes and rheumatoid arthritis as well as other diseases involving fibrosis, such as Alzheimer’s, Ostrov said.

Additional research will continue to explore the compound’s effectiveness in animals and humans.

-----

Source: University of Florida

Article Tools

Share & Save Options

Discussion

There are 0 discussion items posted.

Join the Discussion

You must be a registered user in order to comment on HPCWire stories.

Members enjoy:

	Access to Special Content, including Podcasts, Webcasts, and Whitepapers and more!
	Ability to take an active role in the discussions that are shaping the HPC technology discipline!
	Special offers available only to HPCWire members!

Become a Registered User Today!

Registered Users Log in Here to Comment

Email Address:	Password (case sensitive)

Remember me	Forgot Password?

RSS Feeds

Feeds by Topic

Feeds by Industry

Feeds by Content Type

Feature Articles

Sun, Fujitsu Deliver Quad-Core SPARC64 Servers

Those of you looking forward to Rock -- Sun's much anticipated 16-core processor originally scheduled for release later this year but now pushed to the second half of 2009 -- don't have to wait for those chips to come out to experience that launch party euphoria. This week Sun and Fujitsu announced the latest of their enterprise line of SPARC-based servers, sporting the new SPARC64 VII chip.
Read More...

The Week in Review

The UK makes a multi-million pound investment in science and computing; the Defense Department funds a HPC software project; and TACC's Ranger shows off its new Opterons. John West recaps those stories and more in our weekly wrap-up.
Read More...

Sun's Fortress Language: Parallelism by Default

If anyone knows how to introduce a new programming language, it's Sun Microsystems. The company's highly successful Java language, which was introduced in 1991, has become ubiquitous in network-centric and embedded computing. Today, there's a whole research team at Sun Labs devoted to programming languages, and the big project there in recent years has been the development of the Fortress programming language. The end game is to "do for Fortran what Java did for C."
Read More...

Read more HPCwire features...

Top Headlines

Biology Enters 'The Matrix' Through New Computer Language

Jul 22 | Harvard Medical School | A team of Harvard Medical School researchers have developed a computer programming language that can be used to model the biomolecular behavior of proteins. Read more...

Nvidia: Larrabee is a Reaction to CUDA

Jul 21 | Custom PC | Nvidia responds to Pat Gelsinger’s comments about CUDA being just a ‘footnote’ in computing history. Read more...

PlayStation Processor Dominates Green Supercomputing

Jul 21 | ElectronicsWeekly.com | Computers based on the Cell processor dominate the world ranking for energy efficient supercomputers, according to the just-published Green500 list. Read more...

More Power7 Details Emerge, Thanks to Blue Waters Super

Jul 21 | IT Jungle | Rumors have been circulating about IBM's future Power7 processor and how the chip fits into NCSA's upcoming "Blue Waters" supercomputer. Read more...

Hello AMD Socket G34

Jul 17 | DailyTech | AMD's 12-core and 8-core processors will get a new home in 2010. Read more...

Read more headlines...

Featured Whitepapers

Improving Performance and Manageability for Seismic Processing and Imaging Applications with Parallel Storage

Jun 05 | | As pressure increases on the upstream seismic processing community to deliver ever-higher levels of productivity and efficiency, a new generation of storage solutions will be required that allow the maximum utilisation of high-performance computing (HPC) Linux cluster resources, together with the minimum of management overhead.

View the White Paper Library

Multimedia

Podcast: Interview with Ben Bennett of ClearSpeed Technology

Today, HPC organizations are requiring substantially more floating point performance to solve real-world problems. In this podcast, Ben Bennett, ClearSpeed General Manager, discusses how acceleration technology can improve the overall performance of standard x86-based systems...