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Inhibition of prostaglandin E2 or thromboxane A2 promotes human aortic smooth muscle cell differentiation
Author(s) -
Adedoyin Oreoluwa Olufunmilayo,
Loftin Charles D
Publication year - 2013
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.27.1_supplement.lb506
Subject(s) - thromboxane , receptor , cyclooxygenase , thromboxane receptor , vascular smooth muscle , agonist , receptor antagonist , endocrinology , prostaglandin , medicine , thromboxane a2 , antagonist , chemistry , biology , platelet , enzyme , biochemistry , smooth muscle
Inhibition of cyclooxygenase‐2 (COX‐2) helps maintain vascular SMC differentiation when treating abdominal aortic aneurysms in a disease model. However, mechanisms of COX‐2‐dependent vascular SMC phenotypic modulation have not been identified. We assessed the hypothesis that COX‐2 induces SMC de‐differentiation by the action of prostaglandin E 2 (PGE 2 ) or thromboxane A 2 (TXA 2 ). METHODS Cultured SMCs were treated with enzyme inhibitors or prostanoid receptor agonists or antagonists. Expression of α‐actin as a differentiation marker was examined by real‐time PCR, western blot or immunocytochemistry; and EIA performed to measure inhibitor effects on PGE 2 production. RESULTS Celecoxib increased α‐actin expression and significantly reduced PGE 2 synthesis in stimulated cells (p < 0.0001; n=3; unpaired Students t‐test). Differentiated cells treated with 1μM PGE 2 showed significant reduction in differentiation (p < 0.05; n=3; one‐way ANOVA), and treatment with 300nM SQ 29548 (TXA 2 receptor antagonist) promoted differentiation. Also, treatment of de‐differentiated cells with 10 μM seratrodast (TXA 2 receptor antagonist) increased α‐actin expression by 52%, while 5μM IBOP (TXA 2 receptor agonist) reduced differentiation compared with untreated controls. CONCLUSION COX‐2 inhibition may increase hASMC differentiation by inhibiting production of PGE 2 or TXA 2 . Funding: NIH HL083122