Biomechanical stress induces novel arterial intima-enriched genes: implications for vascular adaptation to stress
Received 16 April 2008; received in revised form 11 December 2008; accepted 19 December 2008. published online 12 February 2009.
Abstract
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.
Summary
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.
aDepartment of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA
bDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
cDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA
dDepartment of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
eDepartment of Veterans Affairs, Vanderbilt University Medical Center, Nashville, TN, USA
fDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Corresponding author. Department of Pathology, Vanderbilt University School of Medicine, 1161 21st Ave. South, CC3321a MCN, Nashville, TN 37232, USA. Tel.: +1 615 936 1098; fax: +1 615 343 7023.
Grants: This work was supported by the National Institutes of Health Training Grant 5T32HL07751 (ALP), Vanderbilt Physician Development Award, Veterans Affairs Career Development Award, and KO8HL84020 from the National Institutes of Health, Bethesda, Maryland (PPY).
Disclosures: This work was also supported by the Pfizer Atorvastatin Research Award (PPY).
ABSTRACT