NYU Langone Cardiology Researcher Awarded Institut de France Grand Prize in Science
Moore, also director of the Cardiovascular Research Center at NYU Langone Health, was honored for her answers to central questions in the field of cardiovascular physiology, including, for instance, how persistent activation of the immune system (chronic inflammation) by excess cholesterol drives the development of plaques in the arteries of patients with atherosclerosis.
The award is conferred annually by the Lefoulon-Delalande Foundation at the Institut de
Moore's research team discovered that the immune system recognizes certain (oxidized) forms of cholesterol using signaling proteins (receptors) designed to detect foreign invaders (e.g. bacteria). This immune response sets off chronic inflammation of the arteries that results in the formation of plaques, which compromise arterial blood flow and can lead to heart attacks. Moore and colleagues also showed that when immune system cells known as macrophages engulf oxidized cholesterol, it can lead to the formation of cholesterol crystals that sound an inflammatory alarm. These intracellular cholesterol crystals trigger a protein group called the NLRP3-inflammasome complex. This complex is responsible for generating the potent pro-inflammatory cytokine interleukin-1b, whose inhibition has been shown in clinical trials to reduce risk of cardiovascular events.
"I am thrilled to receive this prize that honors the work carried out by my research team over the last two decades," said Moore. "It has been an honor to work with such talented trainees and world-class colleagues in pursuit of answers to why chronic inflammation develops in response to hyper-cholesterolemia and drives cardiovascular diseases that place such a burden on millions of patients globally."
In other work, Moore and colleagues revealed the role of a molecule called netrin-1 in causing macrophages to accumulate in atherosclerotic plaques and fat (adipose) tissue of obese individuals to drive a vicious cycle of chronic inflammation, insulin resistance, and cardiometabolic disease. Moore also made discoveries on the role of tiny RNA molecules in regulating the pathways that control cholesterol levels in cells and the blood.
She showed that these "microRNAs" can repress the pathways that help cells rid themselves of excess cholesterol, resulting in the accumulation of cholesterol-laden immune cells in plaques and the development of atherosclerotic disease. Importantly, she found that microRNAs, in particular miR-33, could be targeted therapeutically to promote the normal balance of cholesterol in the body.
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SOURCE NYU Langone Health System
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