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International Journal of Inflammation
Volume 2011 (2011), Article ID 176412, 10 pages
http://dx.doi.org/10.4061/2011/176412
Research Article

Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks

1Department of Agricultural and Biological Engineering, Mississippi State University, Mississippi State, MS 39762, USA
2Life Science and Biotechnology Institute, Mississippi State University, Mississippi State, MS 39762, USA
3Department of Basic Sciences, Mississippi State University, Mississippi State, MS 39762, USA
4Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA

Received 7 March 2011; Revised 6 June 2011; Accepted 16 June 2011

Academic Editor: Adrian Chester

Copyright © 2011 James N. Warnock et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The study aimed to identify mechanosensitive pathways and gene networks that are stimulated by elevated cyclic pressure in aortic valve interstitial cells (VICs) and lead to detrimental tissue remodeling and/or pathogenesis. Porcine aortic valve leaflets were exposed to cyclic pressures of 80 or 120 mmHg, corresponding to diastolic transvalvular pressure in normal and hypertensive conditions, respectively. Linear, two-cycle amplification of total RNA, followed by microarray was performed for transcriptome analysis (with qRT-PCR validation). A combination of systems biology modeling and pathway analysis identified novel genes and molecular mechanisms underlying the biological response of VICs to elevated pressure. 56 gene transcripts related to inflammatory response mechanisms were differentially expressed. TNF-α, IL-1α, and IL-1β were key cytokines identified from the gene network model. Also of interest was the discovery that pentraxin 3 (PTX3) was significantly upregulated under elevated pressure conditions (41-fold change). In conclusion, a gene network model showing differentially expressed inflammatory genes and their interactions in VICs exposed to elevated pressure has been developed. This system overview has detected key molecules that could be targeted for pharmacotherapy of aortic stenosis in hypertensive patients.