Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks
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...
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Series: | International Journal of Inflammation |
Online Access: | http://dx.doi.org/10.4061/2011/176412 |
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doaj-2ffc0288c7aa4a538a27bcfbe6ee08352020-11-24T21:43:04ZengHindawi LimitedInternational Journal of Inflammation2042-00992011-01-01201110.4061/2011/176412176412Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene NetworksJames N. Warnock0Bindu Nanduri1Carol A. Pregonero Gamez2Juliet Tang3Daniel Koback4William M. Muir5Shane C. Burgess6Department of Agricultural and Biological Engineering, Mississippi State University, Mississippi State, MS 39762, USADepartment of Basic Sciences, Mississippi State University, Mississippi State, MS 39762, USADepartment of Agricultural and Biological Engineering, Mississippi State University, Mississippi State, MS 39762, USALife Science and Biotechnology Institute, Mississippi State University, Mississippi State, MS 39762, USADepartment of Agricultural and Biological Engineering, Mississippi State University, Mississippi State, MS 39762, USADepartment of Animal Sciences, Purdue University, West Lafayette, IN 47907, USALife Science and Biotechnology Institute, Mississippi State University, Mississippi State, MS 39762, USAThe 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.http://dx.doi.org/10.4061/2011/176412 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
James N. Warnock Bindu Nanduri Carol A. Pregonero Gamez Juliet Tang Daniel Koback William M. Muir Shane C. Burgess |
spellingShingle |
James N. Warnock Bindu Nanduri Carol A. Pregonero Gamez Juliet Tang Daniel Koback William M. Muir Shane C. Burgess Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks International Journal of Inflammation |
author_facet |
James N. Warnock Bindu Nanduri Carol A. Pregonero Gamez Juliet Tang Daniel Koback William M. Muir Shane C. Burgess |
author_sort |
James N. Warnock |
title |
Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks |
title_short |
Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks |
title_full |
Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks |
title_fullStr |
Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks |
title_full_unstemmed |
Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks |
title_sort |
gene profiling of aortic valve interstitial cells under elevated pressure conditions: modulation of inflammatory gene networks |
publisher |
Hindawi Limited |
series |
International Journal of Inflammation |
issn |
2042-0099 |
publishDate |
2011-01-01 |
description |
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. |
url |
http://dx.doi.org/10.4061/2011/176412 |
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