Cyclical strain increases monocyte chemotactic protein-1 secretion in human endothelial cells.
The effects of mechanical strain on monocyte chemotactic protein-1 (MCP-1) secretion were examined on human endothelial cells (ECs) grown on a flexible membrane base. MCP-1 release into culture medium from strained ECs was demonstrated to be time and strain dose dependent. Northern blot analysis demonstrated a mainly serum-independent 1.8-fold induction of MCP-1 mRNA levels in ECs strained at 15 kPa compared with unstrained controls. ECs treated with actinomycin D abolished this strain-induced expression. Strained ECs at the periphery of wells showed higher MCP-1 gene expression than ECs at the center. Pretreatment of ECs with either cytochalasin D or phalloidin did not abolish strain-induced gene expression. ECs pretreated with stretch-activated ion channel blocker gadolinium or with ryanodine to deplete intracellular stored Ca2+ strongly inhibited the strain-induced MCP-1 levels. We conclude that 1) cyclical strain can modulate the secretion of MCP-1 in a dose-dependent manner, 2) strain-induced MCP-1 production is mediated by increasing MCP-1 mRNA levels via transcription, 3) cytoskeletal rearrangement is not essential for this strain-induced MCP-1 expression, and 4) both Ca2+ influx via stretch-activated ion channels and intracellular Ca2+ release contribute to the strain-induced effect. Such strain-induced MCP-1 secretion might contribute to the trapping of monocytes in the subendothelial space to initiate atherogenesis.
Wung
B S
BS
Cardiovascular Division, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Cheng
J J
JJ
Chao
Y J
YJ
Lin
J
J
Shyy
Y J
YJ
Wang
D L
DL
D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D013314:Stress, Mechanical; D013997:Time Factors
D018932:Chemokine CCL2; D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D002118:Calcium