Department of Internal Medicine

UI Cardiovascular Research Center Receives $11.4 Million NIH Renewal

3/26/2003

A University of Iowa Roy J. and Lucille A. Carver College of Medicine cardiovascular research program now in its fourth decade has received its seventh consecutive grant renewal from the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH). The five-year, nearly $11.4 million grant was effective Jan. 1 and will help support studies to understand how the nervous system affects the heart and circulation, especially in relation to heart attacks, high blood pressure, stroke, depression and obesity.

Francois Abboud, M.D., the Edith King Pearson Professor of Cardiovascular Research, UI professor of internal medicine and physiology and biophysics, and UI associate vice president for health affairs, has been principal investigator of the program since its inception in 1971. With this latest funding, the program, known as the "Integrative Neurobiology of Cardiovascular Regulation," has received more than $66 million in support to date from the NIH.

The UI program is one of the longest running program project grants by the same principal investigator in the NHLBI and the first major interdepartmental intercollegiate research program in the UI College of Medicine, Abboud said.

"It is, first and foremost, a team effort," said Abboud, who also is director of the UI Cardiovascular Research Center, which oversees the program. "Dozens of investigators have contributed to its success."

Some of the senior UI researchers who have provided scientific leadership over the years include the late Michael Brody, Melvin Marcus, Alan Kim Johnson, Allyn Mark, Donald Heistad, Gerald DiBona, Philip Schmid, William Talman, Kevin Campbell, Michael Welsh and Mark Chapleau. Others now are leading programs at other institutions.

"The team includes basic scientists and clinician-scientists. Throughout the program, we have maintained the link between investigating the basic molecular fundamentals and studying integrated mechanisms of disease in patients," Abboud said. "This approach has resulted in the discovery of drugs that have dramatically reduced cardiovascular risks and mortality.

"That strength is what makes us unique and likely contributes to why we have been judged to merit the NIH support for all these years," he added.

The focus of the UI research is on the cause of excessive nerve activity from the brain. This activity worsens heart failure and increases mortality from heart attacks. The goal is to eliminate the excessive activity and thus reduce death from heart disease.

Active projects within the program are divided into three broad groups relating to how the nervous system and cardiovascular system interact: sensory activity within the brain itself; sensory input from the heart to the brain; and neural output from the brain to blood vessels.

Two projects that examine central brain functioning have these goals:

• To understand how brain chemicals are involved in depression, which is a major risk factor for heart disease. This project examines how chemical changes that occur during depression may influence the outcome of a heart attack or cause irregular heartbeat or function. The impact of depression on heart disease has been compared to the impact of smoking on heart disease. (Principal investigator: Alan Kim Johnson, Ph.D., the F. Wendell Miller Distinguished Professor of Psychology and Pharmacology)
• To understand how angiotensin, a hormone produced in the brain, regulates blood volume and pressure. Investigators seek to localize the tiny region in the brain where the hormone contributes to hypertension (high blood pressure). By pinpointing this specialized area, researchers may eventually be able to target it for chemical treatment instead of treating the entire brain with drugs. (Principal investigator: Robin Davisson, Ph.D., UI assistant professor of anatomy and cell biology and radiation oncology)

Two other projects focus on the nerves that send signals from the heart to the brain and have these goals:

• To identify the molecules that affect how nerves in the heart deliver information to the brain to regulate circulation. In particular, this project studies the ability of the nerves to sense "stretch" -- when the heart is loaded with fluid -- or sense that a weak part of the heart is preventing it from contracting properly. This information ultimately will help researchers correct defects in the molecules of people who have high blood pressure or, conversely, have low blood pressure and faint easily. (Principal investigator: Abboud)
• To identify the chemicals that increase excitation of nerve endings, or sensors, in the heart and thereby raise blood pressure. These sensors can react to changes in the chemical environment of the heart. Specifically, they can be activated by reactive-oxygen and cause hypertension and heart attacks. (Principal investigator: Mark Chapleau, Ph.D., UI associate professor of internal medicine and a researcher with the Iowa City Veterans Affairs Medical Center (VAMC))

The final two projects are related to the sympathetic nervous system, which manages the output from the brain to primarily the blood vessels, and focus on these goals:

• To study the role of calcitonin gene-related peptide (CGRP) in protecting the brain from vasospasm (severe constriction of the arteries that feed the brain) or stroke after a subarachnoid hemorrhage. Previous research in this project area showed that CGRP located at the end of nerves close to blood vessels is depleted when a person has a stroke due to this type of hemorrhage. Scientists hope to identify the genes that regulate the presence of CGRP and understand why its production is halted or greatly reduced in people who have a stroke. (Principal investigator: Andrew Russo, Ph.D., UI professor of physiology and biophysics)
• To investigate why some people who are obese have high blood pressure and others who also are obese do not. In people with obesity, the sympathetic nervous system is "hyped up." While this can lead to increased constriction of blood vessels and, thus, high blood pressure, it does not always negatively affect the vessels. Researchers seek to understand why abnormal regulation occurs only in some people. (Principal investigator: William Haynes, M.D., UI associate professor of internal medicine and a researcher with the Iowa City VAMC)

In addition to the six projects, the program involves essential expertise from three core facilities at the UI: the Gene Transfer Vector Core (directed by Beverly Davidson, Ph.D., the Roy J. Carver Professor of Internal Medicine), the Transgenic Animal Facility (directed by Curt Sigmund, Ph.D., UI professor of internal medicine and physiology), and the Molecular Biology, Immunocyto-histochemistry and Imaging Core (directed by Ramesh Bhalla, Ph.D., UI professor of anatomy and cell biology, and Ram Sharma, Ph.D., UI research scientist in anatomy and cell biology).

DiBona, Heistad and Talman also are researchers and staff physicians with the Iowa City VAMC

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