Texas Biomedical Research Institute Staff Scientist Dr. Genesio Karere was recently awarded a $609,568 grant from the National Institutes of Health to study and identify molecular mechanisms underlying early atherosclerosis. Atherosclerosis is a thickening of the walls of arteries caused by high levels of "bad" cholesterol in the blood, which leads to cardiovascular disease and stroke. According to Science Daily, by 2030, approximately 116 million people in the U.S. will have some form of cardiovascular disease, the leading cause of death in the United States. Understanding early onset atherosclerosis could facilitate the development of early diagnostics and interventions.
"It's important to understand how and why atherosclerosis develops," Karere explained. "If we can treat atherosclerosis in the early stages, we will be saving millions of lives."
The study will begin by analyzing tissue samples from baboons, which are genetically similar to humans and exhibit many of the same chronic disease responses. This is the first study with nonhuman primates focusing on identifying molecular mechanisms underlying the early onset stages of the disease. Scientists have collected arteries from baboons involved in previously controlled research studies, where they were fed a high fat, high cholesterol diet for two years. Researchers will determine how many of these arteries developed atherosclerotic lesions and analyze the molecular mechanisms leading to the development of these lesions. Scientists will also use CRISPR-Cas9 technology to edit genes that are identified as candidate genes to find MicroRNA interactions involved in the development of atherosclerosis.
Karere said the findings in the baboon could be translated to humans. He explained that most human studies have focused on semi-clinical late stage atherosclerosis, because it is not possible to collect samples and run studies at the early stages of atherosclerosis in a healthy human. Most humans with early onset atherosclerosis are considered to be relatively healthy and unaware of the issue until it has reached the late stages and has developed into cardiovascular disease. Additionally, it is difficult to control a person's diet in the strict manner necessary to capture valid scientific data.
By analyzing these tissue samples and identifying the molecular mechanisms involved in the development of early onset atherosclerosis, scientists could identify ways in which we can diagnose atherosclerosis sooner, allowing for earlier interventions. By analyzing microRNA interactions, Karere and his team are also looking for candidate genes that could serve as targets for drug therapies.
"This work has not been done elsewhere, but because we have the baboon resources, we can do it," Karere explained. "We cannot over emphasize how important this is... how many lives we will be able to save if we will be able to treat people in the early stages of this disease to improve human life."
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