Regulation of the atheroma-enriched protein, SPRR3, in vascular smooth muscle cells through cyclic strain is dependent on integrin alpha1beta1/collagen interaction.

Pyle AL, Atkinson JB, Pozzi A, Reese J, Eckes B, Davidson JM, Crimmins DL, Young PP
Am J Pathol. 2008 173 (5): 1577-88

PMID: 18832573 · PMCID: PMC2570146 · DOI:10.2353/ajpath.2008.080042

Atherosclerotic plaques express high levels of small proline-rich repeat protein (SPRR3), a previously characterized component of the cornified cell envelope of stratified epithelia, where it is believed to play a role in cellular adaptation to biomechanical stress. We investigated the physiological signals and underlying mechanism(s) that regulate atheroma-enriched SPRR3 expression in vascular smooth muscle cells (VSMCs). We showed that SPRR3 is expressed by VSMCs in both human and mouse atheromas. In cultured arterial VSMCs, mechanical cyclic strain, but neither shear stress nor lipid loading induced SPRR3 expression. Furthermore, this upregulation of SPRR3 expression was dependent on VSMC adherence to type I collagen. To link the mechanoregulation of SPRR3 to specific collagen/integrin interactions, we used blocking antibodies against either integrin alpha1 or alpha2 subunits and VSMCs from mice that lack specific collagen receptors. Our results showed a dependence on the alpha1beta1 integrin for SPRR3 expression induced by cyclic strain. Furthermore, we showed that integrin alpha1 but not alpha2 subunits were expressed on VSMCs within mouse lesions but not in normal arteries. Therefore, we identified the enrichment of the mechanical strain-regulated protein SPRR3 in VSMCs of both human and mouse atherosclerotic lesions whose expression is dependent on the collagen-binding integrin alpha1beta1 on VSMCs. These data suggest that SPRR3 may play a role in VSMC adaptation to local biomechanical stress within the plaque microenvironment.

MeSH Terms (18)

Animals Atherosclerosis Collagen Humans Integrin alpha1beta1 Lipids Mice Mice, Inbred C57BL Models, Biological Muscle, Smooth, Vascular Myocytes, Smooth Muscle Peptides Proline-Rich Protein Domains Protein Binding Protein Transport Stress, Mechanical Transcription, Genetic Up-Regulation

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