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2.24.2015

Researchers Find Key Mechanism Leading to Vascular Calcification

A University of Miami Miller School of Medicine research team has uncovered a key mechanism in the development of vascular calcification, or hardening of the arteries, valves or plaque – a disorder that affects millions of people.

“We have identified a clear linkage between a specific microRNA molecule, which is naturally produced by the body, and vascular calcification,” said Lina A. Shehadeh, Ph.D., assistant professor of medicine in the Cardiovascular Division and investigator in the Miller School’s Interdisciplinary Stem Cell Institute. “As people age, the body produces less of this microRNA and calcification of the blood vessels increases.”

That groundbreaking finding could have significant clinical implications in potentially preventing or reversing hardening of the arteries and valves, according to Shehadeh, who was the lead author on a study published in the prestigious journal Cardiovascular Research. “MicroRNAs can easily be injected into the body,” she said. “While further laboratory studies and clinical trials are needed, we can hypothesize that raising the levels of this microRNA could slow or even reverse the process of vascular calcification.”

About 787,000 Americans died of cardiovascular disease in 2011, according to the most recent statistics from the American Heart Association, which estimates that more than 85 million Americans are living with some form of cardiovascular disease or the after-effects of stroke. Vascular calcification is not only prevalent in cardiovascular disease patients, but also in patients with Type II diabetes and chronic kidney disease as well as in the aged population.

Shehadeh’s three-year research project – which focused on how a microRNA regulates calcification of bone marrow-derived mesenchymal stem cells and aortic smooth muscle cells – was funded by grants from the National Institute on Aging, the State of Florida, the Florida Heart Research Institute, and the American Federation for Aging Research.

“Artery walls consist mainly of smooth muscle cells, but over time, the smooth muscle cells can begin growing abnormally,” she said. “When they start dividing and migrating, plaques form, making it more difficult for blood to flow through them. Those blockages can cause clots to form, further blocking blood flow, and pieces of plaque can actually break off and move to smaller vessels, blocking them entirely.”

Shehadeh added that people who have high cholesterol or are overweight are at high risk for vascular calcification, and that risk increases with age. “While certain medicines can slow the process, currently there are no treatments to reverse the calcification once it has occurred,” she said.

Shehadeh’s study, “MiR-30e Targets IGF2-Regulated Osteogenesis in Bone Marrow Derived Mesenchymal Stem Cells, Aortic Smooth Muscle Cells and ApoE-/- Mice,” is published online. The first author is Wen Ding, a Ph.D. candidate in the Department of Molecular and Cellular Pharmacology and a recent recipient of a pre-doctoral fellowship from the American Heart Association. Miller School co-authors are Jihe Li, Ph.D.; Jayanti Singh, Ph.D.; Razan Alif, M.S.; Roberto I. Vazquez-Padron, Ph.D., associate professor of surgery; Samirah A. Gomes, M.D., Ph.D.; and Joshua M. Hare, M.D., Director of the Interdisciplinary Stem Cell Institute. The collaborative research project involved the Department of Molecular and Cellular Pharmacology, Interdisciplinary Stem Cell Institute, Cardiovascular Division, Department of Surgery and the Vascular Biology Institute.

“The microRNA we identified regulates other molecules, such as Insulin Growth Factor II, that have been associated with age and calcification,” Shehadeh said. “Using various genetic animal models, we are planning the next studies to learn more about this key process. Importantly, we are active in establishing microRNA delivery methods that can eventually be used in humans.”

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