Altered proliferative responses of dermal fibroblasts to @entity2533 may contribute to chronic venous stasis XXXX .

@entity1 @entity852 @entity1066 @entity2533 @entity4096 @entity7881 @entity291
PURPOSE: Venous @entity1066 fibroblasts demonstrate decreased proliferative responses to growth factor stimulation, suggesting cellular senescence. However, the role of @entity4096 ( @entity4096 ) disease progression and extracellular matrix (ECM) proteins in agonist-induced cellular proliferation is ill-defined. We hypothesize that @entity4096 -induced fibroblast proliferative resistance to growth factors worsens with disease progression and is regulated by the composition of ECM. METHODS: Fibroblast explants were isolated from biopsy specimens from two @entity1 without @entity4096 and 16 @entity1 with @entity4096 of the lower @entity291 (LC) and @entity7881 ( @entity7881 ) and stratified according to CEAP disease severity: non- @entity4096 (NC; n = 2), class 2-3 (n = 5), class 4 (n = 5), class 5 (n = 3), and class 6 (n = 3). Proliferation experiments were standardized with a neonatal foreskin fibroblast cell line (HS68). A 10-day course and dose response experiment with 0, 0.5, 1.0, 2.5, 5, 10, and 20 ng/mL of @entity2533 ( @entity2533 ) demonstrated maximal cell proliferation at 5 ng/mL of @entity2533 on day 4. Under these conditions, @entity4096 dermal fibroblasts were challenged with and without @entity2533 and evaluated for proliferative responses on plates coated with @entity852 , collagen, and fibronectin. RESULTS: No differences in unstimulated proliferation were observed in @entity7881 and LC fibroblasts from @entity1 with class 2-3 disease and @entity7881 fibroblasts from @entity1 with class 4 and 5 disease, compared with NC and HS68 cells. LC fibroblasts from @entity1 with class 4 disease (P <.05) and class 5 disease (P <.001), and LC (P <.001), and @entity7881 fibroblasts from @entity1 with class 6 disease (P <.001) proliferated to a lesser degree than did NC and HS68 cells. The diminished proliferation observed in class 4 LC cells was reversible with @entity2533 stimulation (P <.004); however, class 5 and class 6 LC and @entity7881 fibroblasts did not respond to stimulation with @entity2533 . Collagen increased proliferation of HS68 cells with (P <.05) and without (P <.01) @entity2533 , compared with cells grown on @entity852 , but did not increase proliferative responses in NC or @entity4096 fibroblasts with and without @entity2533 . Similarly, fibronectin increased proliferation of HS68 cells (P <.05) compared with cells grown on @entity852 , but did not alter proliferation in @entity4096 fibroblasts. Fibronectin did seem to inhibit @entity2533 -induced proliferation observed in class 4 LC cells. CONCLUSION: These data indicate that clinical disease progression correlates with cellular dysfunction. Fibroblasts from @entity1 with class 2-3 disease retain their unstimulated and agonist- induced proliferative capacity, compared with NC and HS68 cells. The onset of inflammatory skin changes (class 4 and class 5 disease) diminishes agonist-induced proliferation, and @entity1066 formation (class 6 disease) severely inhibits it. In addition, the composition of ECM does not affect @entity2533 -induced proliferation of fibroblasts in @entity4096 .
