Salicylates and vascular smooth muscle cell proliferation: molecular mechanisms for cell cycle arrest.
Salicylates are effective prophylactic treatment strategies for myocardial infarction and ischemic strokes. Recent evidence suggests that high doses of salicylates may exert direct, platelet-independent effects on the vascular wall. Salicylate and aspirin, in concentrations between 1 and 5 mM, effectively inhibit vascular smooth muscle cell proliferation and DNA synthesis without inducing cellular toxicity or apoptosis. This inhibition is associated with effects on specific cell-cycle regulatory molecules, and may proceed via downregulation of the transcription factor, nuclear factor (NF)-kappaB. High-dose salicylates and selective NF-kappaB inhibitors may, therefore, play an important role in the management of vascular proliferative disorders.
Marra
D E
DE
Vascular Medicine Unit, Cardiovascular Division, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Liao
J K
JK
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000502:physiology; D012459:Salicylates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D012459:Salicylates; D001241:Aspirin