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Manipulating the Plasticity of Smooth Muscle Cells to Regulate Vascular Calcification

1 Department of Agricultural and Biological Engineering, Mississippi State University, Mississippi State, MS, United States
2 Department of Biomolecular Sciences, University of Mississippi School of Pharmacy, University, MS, United States

Cardiovascular complications are one of the leading causes of death in patients with kidney disease or diabetes. Vascular calcification (VC) was once considered a passive process resulting from elevated calcium-phosphate interactions, but is now considered an active cell-mediated process. VC can affect quality of life because healthy arteries harden analogously to bone development leading to hypertension and compromised structural integrity. Based on previous literature, the in vitro model was developed by culturing human primary aortic smooth muscle cells with 3-mmol inorganic phosphate (Pi) and sodium to induce calcification. The in vitro model was then used to prompt VC and promote the genetic switching from healthy smooth muscle cells to osteoblast-like cells through manipulation of the cells’ plasticity. The in vitro model examined the Wnt signaling pathway in VC and Sclerostin’s ability to block activation of the pathway. Atomic absorption spectroscopy, Western blot, and Polymerase chain reaction (PCR) analysis revealed that the model was capable of inducing VC, up-regulating the osteogenic differentiation markers runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 2 (BMP2), and down-regulating α-smooth muscle actin activity. Under the same methods, it was revealed that Sclerostin was capable of recovering α-smooth muscle actin activity in calcification media and able to down-regulate the osteogenic differentiation marker Runx2. This study proved the effectiveness of the in vitro model to induce calcification of healthy vascular smooth muscle cells and Sclerostin’s ability to be used as a potential therapeutic target for VC.
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Keywords Smooth muscle cells; vascular calcification; mesenchymal stem cells; plasticity; α-smooth muscle actin

Citation: Kelsey M. McArthur, Amber M. Kay, Jenna A. Mosier, Joshua N. Grant, James A. Stewart, C. LaShan Simpson. Manipulating the Plasticity of Smooth Muscle Cells to Regulate Vascular Calcification. AIMS Cell and Tissue Engineering, 2017, 1(3): 165-179. doi: 10.3934/celltissue.2017.3.165

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Copyright Info: 2017, C. LaShan Simpson, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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