Induction of Heme Oxygenase-1 Expression Inhibits Platelet-Dependent Thrombosis
dc.contributor.author | Peng, Lin | en_US |
dc.contributor.author | Mundada, Lakshmi | en_US |
dc.contributor.author | Stomel, Joshua M. | en_US |
dc.contributor.author | Liu, Jason J. | en_US |
dc.contributor.author | Sun, Jinhong | en_US |
dc.contributor.author | Yet, Shaw-Fang | en_US |
dc.contributor.author | Fay, William P. | en_US |
dc.date.accessioned | 2009-07-10T19:12:59Z | |
dc.date.available | 2009-07-10T19:12:59Z | |
dc.date.issued | 2004-08-01 | en_US |
dc.identifier.citation | Peng, Lin; Mundada, Lakshmi; Stomel, Joshua M.; Liu, Jason J.; Sun, Jinhong; Yet, Shaw-Fang; Fay, William P. (2004). "Induction of Heme Oxygenase-1 Expression Inhibits Platelet-Dependent Thrombosis." Antioxidants & Redox Signaling 6(4): 729-735 <http://hdl.handle.net/2027.42/63386> | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/63386 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=15242554&dopt=citation | en_US |
dc.description.abstract | Heme oxygenase-1 (HO-1) plays a key role in protecting tissue from oxidative stress. Although some studies implicate HO-1 in modulating thrombosis after vascular injury, the impact of HO-1 on the rate of clot formation in vivo is poorly defined. This study examined the potential function of HO-1 in regulating platelet-dependent arterial thrombosis. Platelet-rich thrombi were induced in C57BL/6J mice by applying 10% ferric chloride to the exposed carotid artery. Mean occlusion time of wild-type mice (n = 10) was 14.6 ± 1.0 min versus 12.9 ± 0.6 min for HO-1-/- mice (n = 11, p = 0.17). However, after challenge with hemin, mean occlusion time was significantly longer in wild-type mice (16.3 ± 1.2 min, n = 15) than HO-1-/- mice (12.0 ± 1.0 min, n = 9; p = 0.021). Hemin administration induced an approximately twofold increase in oxidative stress, measured as plasma thiobarbituric acid reactive substances. Immunohistochemical analysis revealed that hemin induced a robust increase in HO-1 expression within the carotid arterial wall. Ex vivo blood clotting within a collagen-coated perfusion chamber was studied to determine whether the accelerated thrombosis observed in HO-1-/- mice was contributed to by effects on the blood itself. Under basal conditions, mean clot formation during perfusion of blood over collagen did not differ between wild-type mice and HO-1-/- mice. However, after hemin challenge, mean clot formation was significantly increased in HO-1-/- mice compared with wild-type controls. These results suggest that, under basal conditions, HO-1 does not exert a significant effect on platelet-dependent clot formation in vivo. However, under conditions that stimulate HO-1 production, platelet-dependent thrombus formation is inhibited by HO-1. Enhanced HO-1 expression in response to oxidative stress may represent an adaptive response mechanism to down-regulate platelet activation under prothrombotic conditions. | en_US |
dc.format.extent | 229494 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Mary Ann Liebert, Inc., publishers | en_US |
dc.title | Induction of Heme Oxygenase-1 Expression Inhibits Platelet-Dependent Thrombosis | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.identifier.pmid | 15242554 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/63386/1/1523086041361677.pdf | |
dc.identifier.doi | doi:10.1089/1523086041361677 | en_US |
dc.identifier.source | Antioxidants & Redox Signaling | en_US |
dc.identifier.source | Antioxidants & Redox Signaling | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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