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Cyclical strain increases monocyte chemotactic protein-1 secretion in human endothelial cells
B S Wung1, J J Cheng, Y J Chao
1Cardiovascular Division, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
The American Journal of Physiology
|April 1, 1996
Summary
Mechanical strain increases monocyte chemotactic protein-1 (MCP-1) secretion from endothelial cells (ECs) by upregulating MCP-1 mRNA transcription. This process involves calcium signaling, not cytoskeletal changes, and may contribute to atherosclerosis.
Area of Science:
- Cell Biology
- Biochemistry
- Cardiovascular Research
Background:
- Monocyte chemotactic protein-1 (MCP-1) is crucial in inflammatory responses.
- Endothelial cells (ECs) play a key role in vascular health and disease.
- Mechanical forces can influence cellular behavior and signaling.
Purpose of the Study:
- To investigate the impact of mechanical strain on MCP-1 secretion in human ECs.
- To elucidate the molecular mechanisms underlying strain-induced MCP-1 production.
- To determine the role of calcium signaling and cytoskeletal elements in this response.
Main Methods:
- Human ECs cultured on flexible membranes were subjected to controlled mechanical strain.
- MCP-1 secretion and mRNA levels were quantified using ELISAs and Northern blots.
- Inhibitors of transcription (actinomycin D), cytoskeleton (cytochalasin D, phalloidin), ion channels (gadolinium), and intracellular calcium (ryanodine) were used.
Main Results:
- Cyclical strain significantly increased MCP-1 secretion and mRNA levels in a time- and dose-dependent manner.
- Strain-induced MCP-1 expression was primarily mediated by transcriptional upregulation.
- Cytoskeletal inhibitors did not affect strain-induced MCP-1 production.
- Inhibition of stretch-activated ion channels and intracellular calcium stores markedly reduced MCP-1 levels.
Conclusions:
- Mechanical strain modulates MCP-1 secretion in ECs through transcriptional regulation.
- Calcium influx via stretch-activated ion channels and intracellular calcium release are critical for strain-induced MCP-1 production.
- The findings suggest a role for mechanical strain in MCP-1 mediated monocyte recruitment and atherogenesis initiation.