In a mouse model, expression of miR-143 and miR-145 was reduced to almost nothing where disease-related proliferation of VSMC had thickened blood vessel walls. These findings suggest that miR-143 and miR-145 - in partnership with myocardin - maintain the normal balance between mature VSMC and their precursors. Thus, researchers believe the drop in miR-143 and miR-145 levels seen in disease settings contributes greatly to vessel wall thickening, but that theory will need to be confirmed by further studies.

In addition, Rochester investigators found that myocardin and SRF activate genes that may influence the rate at which the brain can remove amyloid beta, the toxic protein that builds up in blood vessels in the brains of patients with Alzheimer's disease. In a February 2009 article in the journal Nature Cell Biology, University of Rochester investigator, Berislav Zlokovic, M.D., Ph.D. found that when SRF and myocardin are active, amyloid beta accumulates in VSMC lining blood vessels. The discovery that miR-145 encourages the expression of myocardin could explain why myocardin may occur in higher levels in Alzheimer's disease, which is turning out to be a problem of "vascular plumbing."

"The finding that a microRNA controls levels of myocardin, the master regulator of VSMC identity and function, forms the starting point in efforts to design new classes of treatment for vascular diseases that represent leading causes of death," said Joseph M. Miano, Ph.D., associate professor within the Aab Cardiovascular Research Institute at the University of Rochester Medical Center, and a study author. He and Srivastava trained together under the direction of renowned muscle biologist Eric Olson at M.D. Anderson Cancer Center in the early 1990s. Miano was also a co-author of the paper on Alzheimer's with Zlokovic. "One of the most important of potential applications for this work would be to deliver miR-145 into vessel walls as a way to normalize levels of myocardin, which would counter vessel wall thickening."

Rochester provided GICD with samples of blood vessels containing lesions with dramatically reduced levels of myocardin. GICD then looked at levels of miR-143 and miR-145 in this disease setting. The team in Rochester also did experiments to show that local delivery of miR-145 in mouse blood vessels leads to elevated expression of myocardin and its target genes.

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