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Scientists Receive $3.5M in Grants to fight Cardiovascular Disease

ALBANY, N.Y., June 2, 2010—Researchers in the Center for Cardiovascular Sciences (CCS) at Albany Medical College have received two large government grants to continue their studies of the basic workings of the cardiovascular system. Harold Singer, Ph.D., professor and director of the CCS, received a 4-year, $1.6 million grant from the National Heart, Lung and Blood Institute (NHLBI), and Mohamed Trebak, Ph.D., associate professor, received a 5-year, $1.9 million grant from the NHLBI.

Both scientists are focused on changes that occur on the molecular level in blood vessel disease (cardiovascular disease)—the number one killer in the United States.

“The basic physiology of the cardiovascular system is understood. But we want to understand heart and vascular disease at the cellular, molecular and genetic levels. This provides new opportunities for improved treatments and better disease prevention,” says Dr. Singer.

For much of his career, Dr. Singer has been focused on muscle cells located in arteries and veins called vascular smooth muscle. Normally, these muscle cells allow arteries and veins to contract and relax regulating blood pressure and blood flow throughout the body. However, abnormal growth of these cells can result in structural changes in blood vessels leading to high blood pressure. “The vessel walls can either lose their elasticity or expand in thickness. In either case, the result can be poor control of blood flow and increased blood pressure,” explains Singer. In the case of another deadly cardiovascular disease, atherosclerosis, abnormal growth of vascular smooth muscle cells contributes to the build-up and rupture of plaques within blood vessels that leads to heart attacks and strokes. He says if they can understand what exactly it is at the cell and molecular levels that is regulating vascular smooth muscle growth, they may be able to identify new targets for drugs to treat these conditions.

Dr. Singer is looking at how vascular smooth muscle cells process signals they receive that stimulate them to grow and migrate in response to vascular injury or disease. He believes that a better understanding of these signals, which include sharp increases in calcium levels inside the cells, will provide insight into the basic mechanisms underlying vascular diseases.

“We are investigating previously undiscovered pathways for regulating calcium levels and calcium effects inside vascular smooth muscle cells—mechanisms that are different from those targeted by currently available calcium channel blockers. These mechanisms could provide targets for new therapeutics that can control calcium or its effects, which in turn controls blood pressure as well as vascular smooth muscle growth and migration,” says Dr. Singer. And, he adds, because these signals are a regulatory system found in all cells and tissues, the information derived from these studies could extend to other processes involving cell growth and motility such as wound healing or angiogenesis (growth of blood vessels).

While Dr. Singer is focused on the processing of calcium signals and the molecular pathways that result in cell growth or migration, Dr. Trebak’s research is focused on the protein channels that these calcium signals use to enter cells and cause disease response in arteries. He says these channels can be thought of as “doorways or pores” that are present on the surface of smooth muscle cells. These pores ordinarily are very well regulated and open and close to allow calcium inside the cell. However, for an unknown reason, sometimes they “go haywire,” opening up more often and letting more calcium in, or actually increasing in number on the surface of the cell so that instead of just a few “pores” there may be hundreds present—all letting calcium in.

“When this happens, we see inappropriate contraction, growth, and migration of vascular cells, all resulting in cardiovascular disease. We want to know, ‘what is the molecular identity of these pores and how do the pores number or activity increase and why?’ If we know the mechanism that guides this process, we might be able to inhibit it with a drug or combination of drugs. Second, if these pathways are turned on and you know which molecules are turning them on by binding to the pore, we can find drugs that interfere with that binding—basically “pore blockers” that could be useful in treating hypertension or atherosclerotic plaque development,” Dr. Trebak says.

At Albany Medical College, one of the nation’s oldest medical schools, basic research scientists work to facilitate discoveries that translate into medical innovations at patients’ bedsides. NIH-funded scientists are conducting research in many exciting areas including infectious disease, biodefense, addiction, cancer, pain, and more.

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