Characterization of Heme Oxygenase in Adult Rodent Platelets

Hean      Zhuang; Marguerite   T.   Littleton-Kearney; Sylvain      Dore

Abstract

Thromboembolism - and its involvement with tissue infarction and ischemic necrosis - continues to be of major importance in the area of vascular biology that affects all areas of clinical medicine. Activated platelets and their aggregations are key initiators in the formation of the thrombus. Several mechanisms have been described to modulate thrombus formation in the circulation, such as prostacyclins and endothelium-derived relaxing factors (the most studied being nitric oxide). Similar to nitrous oxide (NO), carbon monoxide (CO) can modulate guanylate cyclase and has been associated with anti-inflammatory and anti-apoptotic activities. Heme oxygenase (HO), in addition to being the ratelimiting enzyme of CO generation, degrades heme, which is a pro-oxidant/pro-inflammatory and generates the antioxidant molecules biliverdin and bilirubin. HO-2 is generally considered to be enriched in the brain. Here, by studying mouse platelets, we showed that it is highly present in wildtype (WT) animals and not detectable in HO-2 knockout mice. A similar finding was observed in female rats. We also investigated whether modification of estrogen levels (naturally occurring, with age, or surgically) and estrogen replacement would affect intraplatelet HO levels. Under these chronic conditions, HO-1 was barely detectable, while HO-2 was consistently stably expressed at high levels. Further investigation into the functional properties of HO itself, heme degradation, and heme bioactive metabolites remains to be conducted to determine the role of HO on platelet dynamics and on microvasculature.

Keywords: blood flow, carbon monoxide, estrogen, hemin, mouse, iron, rat

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