Vascular Heme Oxygenase-1 Induction Suppresses Microvascular Thrombus Formation In Vivo
| Autor: | Michael D. Menger, R. Bordel, Brigitte Vollmar, W. Schareck, Nicole Lindenblatt |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
Metalloporphyrins medicine.medical_treatment Intraperitoneal injection Protoporphyrins Ferric Compounds Antioxidants Microcirculation Mice chemistry.chemical_compound Chlorides In vivo medicine Animals Chromans Enzyme Inhibitors Thrombus Muscle Skeletal Heme Mice Knockout Membrane Proteins Bilirubin Thrombosis medicine.disease Cell biology Mice Inbred C57BL Heme oxygenase P-Selectin Biochemistry chemistry Enzyme Induction Heme Oxygenase (Decyclizing) Cremaster muscle Hemin Cardiology and Cardiovascular Medicine Heme Oxygenase-1 |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 24:601-606 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000118279.74056.8a |
| Popis: | Objective— By heme degradation, heme oxygenase-1 (HO-1) provides endogenous carbon monoxide and bilirubin, both of which play major roles in vascular biology. The current study aimed to examine whether induction of HO-1 and its byproducts modulate the process of microvascular thrombus formation in vivo. Methods and Results— In individual microvessels of mouse cremaster muscle preparations, ferric chloride-induced thrombus formation was analyzed using intravital fluorescence microscopy. When mice were pretreated with an intraperitoneal injection of hemin, a HO-1 inducer, immunohistochemistry and Western blot protein analysis of cremaster muscle tissue displayed a marked induction of HO-1. In these animals, superfusion with ferric chloride solution induced arteriolar and venular thrombus formation, which, however, was significantly delayed when compared with thrombus formation in animals without HO-1 induction. The delay in thrombus formation in hemin-treated mice was completely blunted by tin protoporphyrin-IX, a HO-1 inhibitor, but not by copper protoporphyrin-IX, which does not inhibit the enzyme. Coadministration of the vitamin E analogue Trolox in HO-1–blocked animals almost completely restored the delay in thrombus formation, implying that, besides CO, the antioxidant HO pathway metabolite bilirubin mainly contributes to the antithrombotic property of HO-1. This was further supported by the fact that bilirubin was found as effective as hemin in delay of ferric chloride-induced thrombus formation. Animals with HO-1 induction revealed reduced P-selectin protein expression in cremaster muscle tissue, which most probably presented the molecular basis for delayed thrombus growth. Conclusion— Local induction of HO-1 activity may be of preventive and therapeutic value for clinical disorders with increased risk of thrombotic events. |
| Databáze: | OpenAIRE |
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