Biochemists receive $1.7 million NIH grant to fight heart disease at the molecular level

SAN ANTONIO (Sept. 17, 2012) — In a window-lined, almost-new laboratory on the campus of the UT Health Science Center San Antonio, a team of biochemists will spend the next four years studying newly discovered causes of cardiovascular disease that could lead to new drugs designed to prevent or reduce the severity of heart ailments.

Reto Asmis, Ph.D., biochemistry professor and associate dean of the Graduate School of Biomedical Sciences, was awarded a four-year, $1.7 million grant from the National Institutes of Health. The grant, which specifically looks at underlying causes of cardiovascular disease at the cellular level, began in July and runs through April 2016.

The laboratory work will be performed at the South Texas Research Facility on the Greehey Academic & Research Campus of the UT Health Science Center San Antonio. The state-of-the-art facility opened last fall.

For the longest time, it was believed that cardiovascular disease could be prevented by blocking within blood vessels the development of oxidative stress, the formation of destructive oxygen species, Dr. Asmis said. Oxidative stress has been repeatedly linked to atherosclerosis, a disease in which plaque builds up inside the arteries, he said. The plaque hardens and narrows the arteries which results in limited flow of blood to one’s organs and other parts of the body. This can result in a heart attack, stroke or even death.

“In the ‘80s and ‘90s, the quest for an anti-oxidant pill became a multi-billion-dollar business,” Dr. Asmis said. “The thought was if we block oxidative stress in blood vessels, you can prevent disease. People started taking a lot of vitamins E and C and beta carotene. Studies eventually showed that in relatively healthy people the protective effects were marginal.”

Dr. Asmis said he and his team became interested in determining whether anti-oxidants required a target other than blood vessels to be effective. They began to look at a novel mechanism involving monocytes (white blood cells formed in bone marrow) that directly links oxidative stress associated with metabolic disorders to heart disease. If Dr. Asmis and his team are correct, their studies may be able to identify the molecular basis for a new causal relationship that explains the well-established associations between metabolic disorders, oxidative stress and cardiovascular disease.

The NIH grant may allow these scientists to develop new drug treatments that could be used to stop or prevent oxidative stress in monocytes in order to prevent cardiovascular disease.

“Findings from the studies proposed here are likely to have a major impact on both preventive and therapeutic strategies for a wide array of diseases – including atherosclerosis, healing after a heart attack, heart failure, and diabetic complications such as renal disease, and impaired wound healing,” Dr. Asmis said.

The research that laid the foundation for this grant is being performed by Hong Seok Kim, M.D., Ph.D., a postdoctoral fellow, and two biochemistry graduate students, Chi Fung Lee, Ph.D., who graduated last year, and Sarah Ullevig, a registered dietitian who graduates this winter.

The title of the grant is “Nox4 and the Redox-Regulation of MKPs in Monocyte Recruitment and Atherosclerosis.” NIH grant 1-HL115858


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