Uniaxial strain upregulates matrix-degrading enzymes produced by human vascular smooth muscle cells.
Arteries remodel in response to environmental changes. We investigated whether mechanical strain modulates production of matrix metalloproteinase (MMP)-2 and -9 by cultured vascular smooth muscle cells (SMC). MMP-2 and MMP-9 expression were tested using human saphenous vein SMC cultured on silicone membranes at rest or subjected to physiological levels (5%) of stationary or cyclical (1 Hz) uniaxial strain. Compared with control, stationary strain significantly increased MMP-2 mRNA levels at all time points, whereas cyclic strain decreased it after 48 h. Both secreted and cell-associated pro-MMP-2 levels were increased by stationary strain at all times (P < 0.01), whereas cyclic strain decreased secreted levels after 48 h (P < 0.02). MMP-9 mRNA levels and pro-MMP-9 protein were increased after 48 h of stationary stretch (P < 0.01) compared with both no strain and cyclic strain. Our study indicates that vascular SMC show a selective response to different types of strain. We suggest that local increases in stationary mechanical strain resulting from stenting, hypertension, or atherosclerosis may lead to enhanced matrix degradation by SMC.
Asanuma
Kazuhiko
K
Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30332, USA.
Magid
Richard
R
Johnson
Chad
C
Nerem
Robert M
RM
Galis
Zorina S
ZS
D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D012501:Saphenous Vein / Q000166:cytology; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000502:physiology
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9