Mechanical strain induces specific changes in the synthesis and organization of proteoglycans by vascular smooth muscle cells.
In the mechanically active environment of the artery, cells sense mechanical stimuli and regulate extracellular matrix structure. In this study, we explored the changes in synthesis of proteoglycans by vascular smooth muscle cells in response to precisely controlled mechanical strains. Strain increased mRNA for versican (3.2-fold), biglycan (2.0-fold), and perlecan (2.0-fold), whereas decorin mRNA levels decreased to a third of control levels. Strain also increased versican, biglycan, and perlecan core proteins, with a concomitant decrease in decorin core protein. Deformation did not alter the hydrodynamic size of proteoglycans as evidenced by molecular sieve chromatography but increased sulfate incorporation in both chondroitin/dermatan sulfate proteoglycans and heparan sulfate proteoglycans (p < 0.05 for both). Using DNA microarrays, we also identified the gene for the hyaluronan-linking protein TSG6 as mechanically induced in smooth muscle cells. Northern analysis confirmed a 4.0-fold increase in steady state mRNA for TSG6 following deformation. Size exclusion chromatography under associative conditions showed that versican-hyaluronan aggregation was enhanced following deformation. These data demonstrate that mechanical deformation increases specific vascular smooth muscle cell proteoglycan synthesis and aggregation, indicating a highly coordinated extracellular matrix response to biomechanical stimulation.
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA. rlee@rics.bwh.harvard.edu
R T
RT
Lee
C
C
Yamamoto
Y
Y
Feng
S
S
Potter-Perigo
W H
WH
Briggs
K T
KT
Landschulz
T G
TG
Turi
J F
JF
Thompson
P
P
Libby
T N
TN
Wight
D001011:Aorta / Q000166:cytology; D058578:Biglycan; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000378:metabolism; D002847:Chromatography, Agarose; D058575:Decorin; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007700:Kinetics; D037181:Lectins, C-Type; D008077:Lipoproteins, LDL / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D011509:Proteoglycans / Q000096:biosynthesis* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013314:Stress, Mechanical; D013997:Time Factors; D015854:Up-Regulation; D053675:Versicans
D058578:Biglycan; D011508:Chondroitin Sulfate Proteoglycans; D002809:Chondroitin Sulfates; D058575:Decorin; D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D037181:Lectins, C-Type; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D012333:RNA, Messenger; D053675:Versicans; C546884:BGN protein, human; C546878:DCN protein, human; C508322:VCAN protein, human; C071927:perlecan