Biomechanical stress induces novel arterial intima-enriched genes: implications for vascular adaptation to stress.
BACKGROUND
The arterial vasculature is subjected to considerably greater biomechanical stress than the venous circulation. This is reflected in the difference in morphology between large arteries and veins, however little is known about the molecular differences that arise as a consequence of biomechanical stress. Previously, we identified a group of arterial intima-enriched (AIE) genes: sciellin, periplakin, SPRR3, envoplakin, galectin 7, and plakoglobin that are functionally related in that they contribute to the stress properties of stratified epithelium. We sought to test our hypothesis that these genes were regulated by biomechanical stress in vascular smooth muscle cells (VSMCs).


METHODS
Immunofluorescence was employed to determine the expression of the AIE genes in saphenous vein coronary artery bypass grafts. Furthermore, we used a model of cyclic stress to determine if the AIE genes were regulated by biomechanical stress in VSMCs in vitro.


RESULTS
Sciellin and periplakin were upregulated in saphenous vein coronary artery bypass grafts after arterialization, but were absent in non-arterialized saphenous veins. Sciellin, SPRR3, and periplakin transcripts were all upregulated (4.67-, 4.95-, 2.77-fold, respectively) by prolonged exposure to cyclic strain (24-72 h), but not at earlier time points.


CONCLUSIONS
These findings suggest a novel role for several human AIE genes in the VSMC response to arterialization and extended cyclic strain.


CONCLUSIONS
Biomechanical stress has long been implicated in vascular pathologies. We report the novel finding of a group of genes, previously studied in stratified epithelium, that were regulated by prolonged cyclic stress in vascular smooth muscle cells. This may have important implications to vascular disease.
Pyle
Amy L
AL
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Li
Bin
B
Maupin
Amanda B
AB
Guzman
Raul J
RJ
Crimmins
Dan L
DL
Olson
Sandy
S
Atkinson
James B
JB
Young
Pampee P
PP
D000222:Adaptation, Physiological; D001011:Aorta / Q000166:cytology; D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D051179:Plakins / Q000235:genetics* / Q000378:metabolism; D012501:Saphenous Vein / Q000378:metabolism / Q000473:pathology; D013314:Stress, Mechanical; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D015415:Biomarkers; D002352:Carrier Proteins; D055233:Cornified Envelope Proline-Rich Proteins; C491674:PPL protein, human; D051179:Plakins; C111281:SCEL protein, human; C112254:SPRR3 protein, human