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Shear stress upregulates PLGF protein expression in an endothelial cell/vascular smooth muscle cell coculture system
Author(s) -
Rashdan Nabil A.,
Lloyd Pamela G.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.683.8
Subject(s) - arteriogenesis , shear stress , downregulation and upregulation , medicine , artery , microbiology and biotechnology , andrology , cardiology , chemistry , biology , biochemistry , angiogenesis , materials science , gene , composite material
Arteriogenesis, the process of collateral artery remodelling in response to upstream occlusion, can preserve blood flow and prevent ischemic injury. Arteriogenesis is thought to be driven primarily by shear stress. Interestingly, mRNA for the arteriogenic protein placenta growth factor (PLGF) is increased in collaterals by upstream arterial ligation. Thus, we hypothesized that PLGF expression is regulated by shear stress. To model coronary collateral flow (CCF), we utilized a coculture system. Human coronary artery smooth muscle cells (HCASMC) were grown on the bottom of porous inserts, and human coronary endothelial cells (HCAEC) on the top. The HCAEC layer was then exposed to shear for 2 h in a cone and plate device. Three time‐averaged shear conditions were tested: 0.7 dyn/cm 2 mimicking normal CCF (NF); 12.4 dyn/cm 2 simulating high CCF post‐stenosis (HF); and no shear (C) (N=5 expts). PLGF protein was significantly higher (~25%) in the HF group than in NF or C starting 8 h post‐shear, and continued to increase (~40%) up to 24 h post‐shear (p<0.05). PLGF mRNA was increased 24 h post‐shear in HCASMC in the HF group, relative to NF and C. Shear did not affect PLGF mRNA in HCAEC. These findings indicate that shear stress modulates PLGF expression in HCASMC. We propose that upregulation of PLGF mRNA by shear in SMC in our model system is endothelium‐dependent and may involve hydrogen peroxide. Funding: NIH R01 HL084494 (PL).