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Physiol. Genomics (November 26, 2002). doi:10.1152/physiolgenomics.00046.2002
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Articles in PresS, published online ahead of print November 26, 2002
Physiol Genomics, 10.1152/physiolgenomics.00046.2002
Submitted on April 23, 2002
Accepted on November 20, 2002

GENDER AND TEMPORAL DEPENDENCE OF THE LEFT VENTRICULAR GENOMIC RESPONSE TO PRESSURE OVERLOAD

Ellen O Weinberg1, Maria Mirotsou1, Joseph Gannon1, Victor J Dzau1, Richard T Lee1, and Richard E Pratt1*

1 Medicine, Brigham and Women's Hospital, Boston, MA, USA

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

To characterize responses of the left ventricle to pressure overload at the genomic level,we performed high-density microarray analysis on individual mouse left ventricles. Male and female mice underwent transverse aortic constriction. At one day and 30 weeks, the left ventricular free wall was harvested and RNA isolated from 27 individual ventricles was analyzed on Mu74Av2 GeneChips, which contain ~12,483 distinct genes. Interestingly, a greater number of genes was regulated in response to acute overload than in response to chronic overload. Hierarchical cluster analysis revealed the presence of several distinct expression profiles. Of these clusters, the majority contained genes that were regulated either in response to acute overload or both acute and chronic overload. In addition, clusters revealing gender specific responses to overload were detected. In summary, the acute and chronic genomic responses to pressure overload are distinct. Moreover, gender modifies these responses. Furthermore, these studies have uncovered several novel and potentially important genes that are regulated in response to overload and may open unrecognized avenues for further functional analysis.




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