[Heme oxygenase-1 inhibits thrombosis under oxidative stress].
OBJECTIVE
To study the potential function and mechanism of heme oxygenase-1 (HO-1) in regulating platelet reactivity and arterial thrombosis.


METHODS
HO-1-deficient (HO-1(-/-)) mice were generated by gene knock-out technique, and the genotyping of the mice was performed by PCR analysis of tail DNA. Thrombus formation was induced by applying FeCl(3) to the exposed carotid artery, and the occlusion time was monitored for each animal. Western blot and chemical assays were used to detect HO-1 and cGMP levels in platelets. Platelet aggregation induced by ADP was also studied.


RESULTS
The difference between mean occlusion time of wild-type mice [(15.56 +/- 1.25) min, n = 16] and HO-1(-/-) mice [(12.85 +/- 0.55) min, n = 14] was not statistically significant. However, after challenge with hemin, which induces HO-1 expression, mean occlusion time was significantly longer in wild-type mice [(16.25 +/- 1.20) min, n = 15] than in HO-1(-/-) mice [(11.96 +/- 0.98) min, n = 19; P < 0.05]. Hemin administration which induced oxidative stress could markedly elevate HO-1 level and cGMP concentration in platelet, while suppress ADP induced platelet aggregation in wild type mice.


CONCLUSIONS
Under conditions that stimulate HO-1 production, platelet-dependent thrombus formation is inhibited by HO-1 through the pathway of cGMP expression. It suggests that enhanced platelet HO-1 expression in response to physiological stress may represent an adaptive response mechanism to down-regulate platelet activation under pro-thrombotic conditions.
Peng
Lin
L
Department of Clinical Examination, Tianjin First Central Hospital, Tianjin 300192, China.
William
Fay
F
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D051547:Heme Oxygenase-1 / Q000097:blood / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D010974:Platelet Aggregation; D013927:Thrombosis / Q000378:metabolism / Q000503:physiopathology*
D051547:Heme Oxygenase-1; D006152:Cyclic GMP