on November 17, 2005
Published online before print November 17, 2005, doi: 10.1161/01.ATV.0000196624.70507.0d
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Submitted on June 15, 2005
Accepted on November 1, 2005
Transcriptional Profiles of Valvular and Vascular Endothelial Cells Reveal Phenotypic Differences. Influence of Shear Stress
Jonathan T. Butcher ;
From the Petit Institute for Bioengineering and Bioscience (J.T.B., T.J., R.M.N.) and Woodruff School of Mechanical Engineering (J.T.B., R.M.N.), Georgia Institute of Technology, Atlanta; Coulter Department of Biomedical Engineering (S.T., G.S., H.J.), and Division of Cardiology, Georgia Tech and Emory University, Atlanta; and Cardiovascular Developmental Biology Center (J.T.B., D.T.), Children’s Research Institute, Medical University of South Carolina, Charleston.
* To whom correspondence should be addressed. E-mail: Robert.nerem{at}ibb.gatech.edu.
Objective--The similarities between valvular and vascular lesions suggest pathological initiation mediated through endothelium, but the role of hemodynamics in valvular endothelial biology is poorly understood.
Methods and Results--Monolayers of porcine aortic endothelial cells (PAECs) or porcine aortic valve endothelial cells (PAVECs) were exposed to 20 dyne/cm2 steady laminar shear stress for 48 hours, with static cultures serving as controls. Multiple microarray comparisons were made using RNA from sheared and control batches of both cell types. More than 400 genes were significantly differentially expressed in each comparison group. The resulting profiles were validated at the transcription and protein level and expression patterns confirmed in vivo by immunohistochemistry. PAVECs were found to be less intrinsically inflammatory than PAECs, but both cell types expressed similar antioxidant and antiinflammatory genes in response to shear stress. PAVECs expressed more genes associated with chondrogenesis, whereas PAECs expressed osteogenic genes, and shear stress had a protective effect against calcification.
Conclusions--Transcriptional differences between PAVECs and PAECs highlight the valvular endothelial cell as a distinct organ system and suggest more attention needs to be given to valvular cells to further our understanding of similarities and differences between valvular and vascular pathology.
Key words: aortic valve • shear stress • inflammation • calcification • endothelial cell
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