Defining the Role of Notch Signaling in Vascular Smooth Muscle Cell Differentiation

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The Ohio State University

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Complications resulting from vascular disease such as atherosclerosis are a major health concern in the United States. Treatments to remove atherosclerotic plaques from occluded blood vessels often result in injury causing aberrant vascular smooth muscle cell (VSMC) proliferation leading to restenosis and vessel occlusion, rendering the procedure ineffective. Methods to prevent restenosis are limited due to the lack of understanding of the signaling pathways involved. The Notch signaling pathway is known to be important in VSMC development and likely contributes to vascular diseases, such as atherosclerosis and arteriosclerosis, and may be involved in the restenosis process. This study will define the actions of Notch signaling, and its interaction with two prominent signaling pathways, Platelet Derived Growth Factor (PDGF), which promotes proliferation and dedifferentiation and Transforming Growth Factor Beta (TGFß), which induces differentiation of VSMC. To investigate Notch signaling in vascular cells, human aortic smooth muscle cells were cultured and treated with pathway activators and inhibitors. RNA and protein was isolated from cultured cells and Western blots and quantitative polymerase chain reactions were used to measure the effects on smooth muscle differentiation markers. Results from this study indicate that PDGF in conjunction with Notch signaling promotes dedifferentiation and TGFß in conjunction with Notch activity promotes differentiation in VSMC. Differentiation and dedifferentiation was reduced when Notch signaling was inhibited. The conclusions from this research study have deepened the understanding of Notch signaling in vascular smooth muscle cells, and can possibly lead to the development of novel drug therapies to prevent restenosis.


Abstract accepted into the Wilbert C. Jordan Student Research Forum hosted by the Student National Medical Association at the 50th Annual Medical Education Conference


Notch Signaling, Vascular Smooth Muscle Cell, Vascular Smooth Muscle Cell Differentiation, Transforming Growth Factor Beta, Restenosis, proliferation, Platelet Derived Growth Factor