HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/H736    most recent 01156.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Metaxa, E. Articles by Kolega, J. Search for Related Content PubMed PubMed Citation Articles by Metaxa, E. Articles by Kolega, J.

Nitric oxide-dependent stimulation of endothelial cell proliferation by sustained high flow

¹Toshiba Stroke Research Center, ²Department of Mechanical and Aerospace Engineering, ³Department of Neurosurgery, ⁴Department of Pediatrics, and ⁵Department of Pathology and Anatomical Sciences, University at Buffalo, State University of New York, Buffalo, New York

Submitted 5 October 2007 ; accepted in final form 10 June 2008

Little is understood about endothelial cell (EC) responses to high flow, which mediate adaptive outward remodeling as well as cerebral aneurysm development. Opposite EC behaviors have been reported in vivo including cell loss during aneurysm initiation and cell proliferation during adaptive outward remodeling. This study aims at elucidating the EC growth response to elevated wall shear stress (WSS) and determining if nitric oxide (NO) is involved. A confluent EC monolayer was subjected to steady-state, laminar flow with WSS ranging from 15 to 100 dyn/cm² for 24 and 48 h. Cells oriented to the direction of the flow with a time course that varied with WSS. At 48 h, all cells were aligned with the flow. EC proliferation was examined using bromodeoxyuridine (BrdU) incorporation. The percentage of proliferating ECs rose linearly from 15 to 50 dyn/cm² to more than sixfold at 50–100 dyn/cm² compared with the accepted physiological baseline of 15–20 dyn/cm². In addition, terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) staining revealed that apoptosis decreased with increasing WSS. These results demonstrate that high WSS stimulates EC proliferation and suppresses apoptosis. Furthermore, immunostaining revealed increased endothelial nitric oxide synthase (eNOS) production with increasing WSS. NOS inhibition with N-nitro-L-arginine methyl ester (L-NAME) drastically reduced the WSS-stimulated proliferation, indicating a critical role of NO production in the stimulation of EC proliferation by high WSS.

high wall shear stress; aneurysm; vascular remodeling; endothelial nitric oxide synthase; apoptosis; cell turnover

This article has been cited by other articles:

				J. A. Plock, N. Rafatmehr, D. Sinovcic, J. Schnider, H. Sakai, E. Tsuchida, A. Banic, and D. Erni Hemoglobin vesicles improve wound healing and tissue survival in critically ischemic skin in mice Am J Physiol Heart Circ Physiol, September 1, 2009; 297(3): H905 - H910. [Abstract] [Full Text] [PDF]