CYCLICAL STRAIN INCREASES MONOCYTE CHEMOTACTIC PROTEIN-1 SECRETION INHUMAN ENDOTHELIAL-CELLS

The effects of mechanical strain on monocyte chemotactic protein-1 (MC P-1) secretion were examined on human endothelial cells (ECs) grown on a flexible membrane base. MCP-1 release into culture medium from stra ined ECs was demonstrated to be time and strain dose dependent. Northe rn blot analysis demonstrated a mainly serum-independent 1.8-fold indu ction of MCP-1 mRNA levels in ECs strained at 15 kPa compared with uns trained controls. ECs treated with actinomycin D abolished this strain -induced expression. Strained ECs at the periphery of wells showed hig her MCP-1 gene expression than ECs at the center. Pretreatment of ECs with either cytochalasin D or phalloidin did not abolish strain-induce d gene expression. ECs pretreated with stretch-activated ion channel b locker gadolinium or with ryanodine to deplete intracellular stored Ca 2+ strongly inhibited the strain-induced MCP-1 levels. We conclude tha t 1) cyclical strain can modulate the secretion of MCP-1 in a dose-dep endent manner, 2) strain-induced MCP-1 production is mediated by incre asing MCP-1 mRNA levels via transcription, 3) cytoskeletal rearrangeme nt is not essential for this strain-induced MCP-1 expression, and 4) b oth Ca2+ influx via stretch-activated ion channels and intracellular C a2+ release contribute to the strain-induced effect. Such strain-induc ed MCP-1 secretion might contribute to the trapping of monocytes in th e subendothelial space to initiate atherogenesis.