VEGF-C mediates cyclic pressure-induced endothelial cell proliferation.
Mechanical forces modulate endothelial cell functions through several mechanisms including regulation of gene transcription. In the present study, gene transcription by human umbilical vein endothelial cells (HUVEC) either maintained under control pressure (that is, standard cell culture conditions equivalent to 0.15 mmHg sustained hydrostatic pressure) or exposed to 60/20 mmHg sinusoidal pressures at 1 Hz were compared using Affymetrix GeneChip microarrays to identify cellular/molecular mechanisms associated with endothelial cell responses to cyclic pressure. Cyclic pressure selectively affected transcription of 14 genes that included a set of mechanosensitive proteins involved in hemostasis (tissue plasminogen activator), cell adhesion (integrin-alpha2), and cell signaling (Rho B, cytosolic phospholipase A2), as well as a unique subset of cyclic pressure-sensitive genes such as vascular endothelial growth factor (VEGF)-C and transforming growth factor (TGF)-beta2. The present study also provided first evidence that VEGF-C, the most highly induced gene under 60/20 mmHg, mediated HUVEC proliferation in response to this cyclic pressure. Cyclic pressure is, therefore, a mechanical force that modulates endothelial cell functions (such as proliferation) by activating a specific transcriptional program.
Shin
Hainsworth Y
HY
Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180-3590, USA.
Smith
Michael L
ML
Toy
Karen J
KJ
Williams
P Mickey
PM
Bizios
Rena
R
Gerritsen
Mary E
ME
D002455:Cell Division; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D010507:Periodicity; D011312:Pressure; D012333:RNA, Messenger / Q000096:biosynthesis; D013314:Stress, Mechanical; D014158:Transcription, Genetic; D042582:Vascular Endothelial Growth Factor C
D016228:Endothelial Growth Factors; D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C