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Current Genomics

Editor-in-Chief

ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

Profiling the Shear Stress of Atherosclerosis; A Genomic View

Author(s): C. Stenson-Cox, V. Barron, B. P. Murphy, P. E. McHugh and T. Smith

Volume 5 , Issue 4 , 2004

Page: [287 - 297] Pages: 11

DOI: 10.2174/1389202043349327

Price: $65

Abstract

Atherosclerosis is a chief cause of heart attack, stroke and death in Western society. It is a disease of the large arteries characterised by the presence of atherosclerotic lesions, often observable as fatty streaks within the first decade of life. A number of factors influence the development and progression of atherosclerosis; however, hemodynamic forces appear to play a critical role in the earliest stages of lesion formation. Significantly, lesions selectively develop in the areas of the vasculature associated with low shear stress, such as at the bends and bifurcations of the arterial tree. In contrast, areas subjected to uniform laminar flow, as found in the straight tubular portions of arteries are considered athero-resistant. Hemodynamic forces influence the transcription of genes within the endothelial cells that line the entire vascular system. Transcriptional changes include the modulation of genes encoding cytokines, adhesion molecules, transcription factors and growth factors. Shear stress-responsive gene expression may underpin the role that hemodynamic forces play in vascular homeostasis and pathophysiology; however, it is not clear exactly how hemodynamic forces influence the genesis and progression of atherosclerosis. DNA microarray technology has recently been employed to identify novel hemodynamic flow-responsive genes and gene families. In the current study we compile such gene expression data from large-scale transcriptomic profiling and examine it within the pathological context of atherosclerosis. By understanding the molecular mechanisms underlying the role that hemodynamic forces play in the pathogenesis of vascular disease it may be possible to identify central mediators of the disease and to design new therapeutic strategies.

Keywords: shear stress, laminar flow, disturbed flow, dna microarray


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