Published Online
on October 6, 2003

A more recent version of this article appeared on October 14, 2003

This Article Full Text (PDF) Data Supplement All Versions of this Article: 108/15/1845    most recent 01.CIR.0000091407.86925.7Av1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Durier, S. Articles by Pratt, R. E. Search for Related Content PubMed PubMed Citation Articles by Durier, S. Articles by Pratt, R. E. Pubmed/NCBI databases GEO DataSet Substance via MeSH Related Collections Remodeling Cell signalling/signal transduction Functional genomics Gene expression Gene regulation Genomics Physiological and pathological control of gene expression Clinical Studies Other Vascular biology

Submitted on November 18, 2002
Revised on July 24, 2003
Accepted on July 26, 2003

Physiological Genomics of Human Arteries. Quantitative Relationship Between Gene Expression and Arterial Stiffness

Séverine Durier PhD, Céline Fassot PhD, Stéphane Laurent MD, PhD, Pierre Boutouyrie MD, PhD, Jean-Paul Couetil MD, Erika Fine MD, Patrick Lacolley MD, PhD, Victor J. Dzau MD, and Richard E. Pratt PhD^*

From the Laboratory of Physiological Genomics, Department of Medicine (V.J.D., R.E.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; the Department of Pharmacology and INSERM EMI 107 (S.D., C.F., S.L., P.B., E.F., P.L.) and the Department of Cardiac Surgery (J.-P.C.), Hôpital Européen Georges Pompidou, Paris, France

^* To whom correspondence should be addressed. E-mail: rpratt{at}rics.bwh.harvard.edu.

Background--Previous genomic studies with human tissues have compared differential gene expression between 2 conditions (ie, normal versus diseased) to identify altered gene expression in a binary manner; however, a potentially more informative approach is to correlate the levels of gene expression with quantitative physiological parameters.

Methods and Results--In this study, we have used this approach to examine genes whose expression correlates with arterial stiffness in human aortic specimens. Our data identify 2 distinct groups of genes, those associated with cell signaling and those associated with the mechanical regulation of vascular structure (cytoskeletal-cell membrane-extracellular matrix). Although previous studies have concentrated on the contribution of the latter group toward arterial stiffness, our data suggest that changes in expression of signaling molecules play an equally important role. Alterations in the profiles of signaling molecules could be involved in the regulation of cell cytoskeletal organization, cell-matrix interactions, or the contractile state of the cell.

Conclusion--Although the influence of smooth muscle contraction/relaxation on arterial stiffness could be controversial, our provocative data would suggest that further studies on this subject are indicated.

Key words: arteries • extracellular matrix • phosphoprotein phosphatase • proteins, cytoskeletal • genomics

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