Abstract
The results of studies that were performed to determine whether cigarette smoking affects platelet function have been controversial, and the effects of nicotine- and tar-free cigarette smoke extract (CSE) on platelet function remain to be determined. The aim of this study was to determine the effect of CSE on platelet aggregation and to clarify the mechanism by which CSE affects platelet function. CSE inhibited murine platelet aggregation induced by 9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U-46619), a thromboxane (TX) A 2 receptor agonist, and that induced by collagen with respective IC 50 values of 1.05 ± 0.14% and 1.34 ± 0.19%. A similar inhibitory action of CSE was also observed in human platelets. CSE inhibited arachidonic acid–induced TXA 2 production in murine platelets with an IC 50 value of 7.32 ± 2.00%. Accordingly, the inhibitory effect of CSE on collagen-induced aggregation was significantly blunted in platelets lacking the TXA 2 receptor compared with the inhibitory effect in control platelets. In contrast, the antiplatelet effects of CSE in platelets lacking each inhibitory prostanoid receptor, prostaglandin (PG) I 2 receptor and PGE 2 receptor subtypes EP 2 and EP 4 , were not significantly different from the effects in respective control platelets. Among the enzymes responsible for TXA 2 production in platelets, the activity of cyclooxygenase (COX)-1 was inhibited by CSE with an IC 50 value of 1.07 ± 0.15% in an uncompetitive manner. In contrast, the activity of TX synthase was enhanced by CSE. The results indicate that CSE inhibits COX-1 activity and thereby decreases TXA 2 production in platelets, leading to inhibition of platelet aggregation.
Highlights
cigarette smoke extract (CSE) Inhibits U-46619- or Collagen-Induced Platelet Aggregation To determine whether cigarette smoke components other than nicotine and tar affect platelet aggregation, we examined the effect of nicotine- and tar-free CSE on aggregation in platelets prepared from WT mice (WT platelets)
The inhibitory effect of CSE on adenosine diphosphate (ADP)-induced platelet aggregation was weak, and its inhibition was only 19.1 Æ 6.3% of control aggregation at a maximum concentration (►Fig. 1D)
We found in a previous study that selective agonists for PGE2 receptor subtypes EP2 and EP4 potently inhibit platelet aggregation.[29]. To determine whether these prostanoid receptors contribute to the inhibitory action of CSE on platelet aggregation, we examined the effect of CSE on U-46619induced aggregation of platelets lacking EP2 (EP2–/– platelets), EP4 (EP4–/– platelets), or IP (IP–/– platelets)
Summary
Inhibition of Platelet Aggregation by Cigarette Smoke Extract Kashiwagi et al e123 platelets. Cigarette smoking potentiated platelet aggregation induced by various stimulants,[7,8] and platelet activity was increased by both the mainstream and sidestream of cigarette smoke.[9] activated platelets from smokers showed spontaneous aggregation[10] and contributed to the augmented strength of blood clots.[11] Among smokers, platelet aggregation was more enhanced in long-term smokers than in short-term smokers.[12] some studies showed an inhibitory effect or no effect of cigarette smoking on platelet function. It was shown that the degree of platelet aggregation in response to collagen was lower in habitual smokers than in nonsmokers.[13] In addition, it was shown that platelet aggregation induced by various stimulants and platelet hemostatic capacity were decreased or unchanged in smokers compared with those in nonsmokers.[14] the effect of cigarette smoking on platelet function remains to be determined
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