Cyclic strain increases protease-activated receptor-1 expression in vascular smooth muscle cells

Area of Science:

• Vascular biology
• Cellular mechanotransduction
• Biomedical engineering

Background:

• Vascular smooth muscle cell (VSMC) functions are modulated by mechanical forces, influencing gene expression.
• Protease-activated receptor-1 (PAR-1) plays a role in vascular health and disease, with its expression potentially affected by mechanical stimuli.

Purpose of the Study:

• To investigate the impact of cyclic strain on PAR-1 expression and function in VSMCs.
• To identify the signaling pathways mediating the effects of cyclic strain on PAR-1.

Main Methods:

• VSMCs were subjected to uniaxial cyclic strain (1 Hz, 20%) on elastic membranes.
• PAR-1 mRNA and protein levels were quantified.
• Cell proliferation assays were used to assess PAR-1 functional activity.
• Inhibitors of various signaling pathways (antioxidants, NADPH oxidase, protein kinases) were employed.

Main Results:

• Cyclic strain significantly increased both PAR-1 mRNA and protein levels (2-fold).
• Strain-induced increase in PAR-1 enhanced thrombin-mediated cell proliferation.
• Antioxidants and NADPH oxidase inhibition blocked the strain-induced PAR-1 upregulation.
• Specific protein kinase inhibitors enhanced strain-induced PAR-1 expression, while others had no effect.

Conclusions:

• Cyclic strain upregulates PAR-1 expression and function in VSMCs, potentially via NADPH oxidase-dependent pathways.
• VSMCs exhibit differential responses to various mechanical forces, with cyclic strain upregulating and shear stress downregulating PAR-1.
• These findings provide a basis for understanding VSMC mechanosensing and signaling.