Effects of aspirin and indomethacin on endothelial cell proliferation in vitro.
OBJECTIVE
Non-steroidal anti-inflammatory drugs (NSAID) are associated with delayed peptic ulcer healing. Ulcer healing is dependent on angiogenesis, which requires endothelial cell (EC) proliferation. The present study aimed to determine whether NSAID and prostaglandin E2 (PGE2) inhibited EC proliferation in vitro.


METHODS
Effects of 50 micro L aspirin (10 micro M-1 mM), indomethacin (10 micro M-1 mM) and PGE2 (1 micro M-0.1 mM) on the proliferation, viability and cell cycle of human dermal microvascular (HuDMEC) and human umbilical vein (HUVEC) EC were assessed using dual staining cell viability, 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide and flow cytometry assays.


RESULTS
Proliferation of HuDMEC and HUVEC was significantly inhibited by 0.1 mM/1 mM indomethacin, 1 mM aspirin and 100 micro M PGE2, with a significant (P < 0.05) increase in EC necrosis with 1 mM indomethacin and 100 micro M PGE2. No effects on cell cycle were demonstrated.


CONCLUSIONS
High concentrations of NSAID inhibit both HuDMEC and HUVEC proliferation in vitro by cytotoxic (indomethacin) or cytostatic (aspirin and indomethacin) mechanisms. Interestingly, PGE2 was also antiproliferative. Inhibition of EC proliferation may prevent angiogenesis at the ulcer site, which may in part explain the delayed ulcer healing associated with NSAID.
Pearce
H R
HR
Academic Unit of Surgery, Division of Clinical Sciences, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK.
Kalia
N
N
Bardhan
K D
KD
Brown
N J
NJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin