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Am J Physiol Heart Circ Physiol (October 11, 2001). doi:10.1152/ajpheart.00292.2001
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Articles in PresS, published online ahead of print October 11, 2001
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00292.2001
Submitted on April 9, 2001
Accepted on October 1, 2001

UP-REGULATION OF MULTIPLE MATRIX COLLAGENS DETECTED BY GENE ARRAY ANALYSIS IN A MODEL OF FLOW INDUCED PULMONARY VASCULAR REMODELING

Meetha Medhora1, Michael Bousamra II2, Daling Zhu1, Lewis Somberg3, and Elizabeth R Jacobs1*

1 Department of Medicine and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, USA
2 Department of Surgery, University of Louisville, Jewish Hospital Heart Institute, Louisville, KY, USA
3 Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA

* To whom correspondence should be addressed. E-mail: ejacobs{at}mcw.edu.

We recently reported localized increased pulmonary arterial resistance, neointimal lesions and medial thickening induced by aorto-pulmonary anastomosis in young pigs. This model was used to investigate changes in expression of genes potentially involved in pulmonary vascular remodeling employing a high throughput Atlas Human Cardiovascular ArrayTM carrying approximately 600 cardiovascular related cDNA sequences. Data were confirmed by Northern analysis, Western blots and histologic examination. Using conditions of lower stringency for hybridization, 56% of the 588 human genes on the array showed visible signal after autoradiography. Approximately 10% of the genes with visible hybridization were altered by shunt-induced high-flow. Extra-cellular matrix and cell adhesion molecules were the most highly represented group of up-regulated genes. To our knowledge, our data are the first to demonstrate flow-induced changes in gene expression using a combination of cross species cDNA-arrays, homologous hybridization, immunospecific protein, and histology. Our observations expand the list of genes as putative candidates in pulmonary vascular remodeling and support the utility of cross-species microarray analysis in such applications.




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