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You are here: Contents > 2006 > Volume 15 Number 1 January 2006 > AORTIC VALVE DISEASE > Differential Immediate-Early Gene Responses to Elevated Pressure in Porcine Aortic Valve Interstitial Cells

Differential Immediate-Early Gene Responses to Elevated Pressure in Porcine Aortic Valve Interstitial Cells

James N. Warnock, Shane C. Burgess, Allen Shack, Ajit P. Yoganathan

Agricultural and Biological Engineering, Mississippi State University, Mississippi State, Georgia Tech/Emory Center for the Engineering of Living Tissues, Atlanta, College of Veterinary Medicine, Basic Science Department, Mississippi State University, Mississippi State, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA

Background and aim of the study: Cardiovascular risk factors are believed to play a role in the pathogenesis of aortic valve disease. In the present study the hypothesis was proposed that elevated pressure would cause a change in the expression of prototypical pro-inflammatory genes. Hence, the expression of MCP-1, osteopontin (OPN), VCAM-1, GM-CSF and PAI-1 was examined using semi-quantitative real-time RT-PCR.
Methods: Porcine aortic valve interstitial cells at passage 1 were exposed to constant pressures of 100, 140, or 170 mmHg or cyclic pressures of 80-120, 120-160, or 150-190 mmHg for 2 h. Static cultures at atmospheric pressure served as controls. Total RNA from pooled experiments was isolated for analysis of gene expression. Single tube primer-mediated RT-PCR was performed directly on the RNA.
Results: Cells responded differently to constant and cyclic pressure. The most notable response was the expression of OPN, which was significantly up-

regulated under steady conditions but down-regulated under cyclic conditions. The opposite was true in VCAM-1 expression, which was significantly down-regulated at 170 mmHg static pressure, but up-regulated at 140 and 170 mmHg mean cyclic pressure. There was no clear proportional correlation between pressure magnitude and expression of MCP-1, GM-CSF, or PAI-1. However, elevated cyclic pressure caused a proportional increase in VCAM-1 expression and a proportional decrease in OPN expression.
Conclusion: Elevated cyclic pressure is a potent stimulus for the up-regulation of VCAM-1 expression and the down-regulation of OPN expression. This demonstrates an association between hypertension and aortic valve stenosis and calcification. The regulation of the chemotactic genes MCP-1 and GM-CSF is not correlated to a change in compressive forces.The Journal of Heart Valve Disease 2006;15:34-42

Differential Immediate-Early Gene Responses to Elevated Pressure in Porcine Aortic Valve Interstitial Cells

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