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Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation by antioxidants.

Abstract

In sickle cell anemia (SCA), inflammatory (i.e., intravascular sickling and transient vasoocclusive) events result in chronic endothelial activation. In addition to sickling behavior, sickle (SS) red blood cells exhibit abnormal interaction with the vascular endothelium, which is considered to have an important role in initiation of vasoocclusion. Upregulation of endothelial adhesion molecules caused by oxidants (and cytokines) may lead to increased SS red cell adhesion. We hypothesize that endothelial activation is indispensable in SS red cell adhesion to the endothelium and that antioxidants will have an inhibitory effect on this interaction. We examined the effect of selected antioxidants in ex vivo mesocecum vasculature, a well-established model that allows measurement of hemodynamic parameters and, by intravital microscopy, can allow quantification of adhesion. We tested antioxidant enzymes (SOD and catalase) and an intravascular SOD mimetic, polynitroxyl albumin (PNA), in the presence of platelet-activating factor (PAF); the latter causes endothelial oxidant generation and endothelial activation, which characterize SCA. In ex vivo preparations, PAF not only induced marked endothelial oxidant generation, it also enhanced SS red cell adhesion, resulting in frequent blockage of small-diameter venules. The adhesion, inversely related to venular diameter, and vasoocclusion were markedly inhibited by antioxidants, resulting in improved hemodynamics. PNA, the most effective antioxidant, also abolished SS red cell adhesion in non-PAF-activated preparations. Thus SS red cell adhesion and related vasoocclusion may be ameliorated by antioxidant therapy with a stable and long-acting molecule (e.g., PNA).

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  • Authors+Show Affiliations

    ,

    Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. kaul@aecom.yu.edu

    , , , ,

    Source

    MeSH

    Anemia, Sickle Cell
    Antioxidants
    Cell Adhesion
    Cells, Cultured
    Erythrocytes
    Humans
    Microcirculation
    Vasoconstriction

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    16443674

    Citation

    Kaul, Dhananjay K., et al. "Inhibition of Sickle Red Cell Adhesion and Vasoocclusion in the Microcirculation By Antioxidants." American Journal of Physiology. Heart and Circulatory Physiology, vol. 291, no. 1, 2006, pp. H167-75.
    Kaul DK, Liu XD, Zhang X, et al. Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation by antioxidants. Am J Physiol Heart Circ Physiol. 2006;291(1):H167-75.
    Kaul, D. K., Liu, X. D., Zhang, X., Ma, L., Hsia, C. J., & Nagel, R. L. (2006). Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation by antioxidants. American Journal of Physiology. Heart and Circulatory Physiology, 291(1), pp. H167-75.
    Kaul DK, et al. Inhibition of Sickle Red Cell Adhesion and Vasoocclusion in the Microcirculation By Antioxidants. Am J Physiol Heart Circ Physiol. 2006;291(1):H167-75. PubMed PMID: 16443674.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation by antioxidants. AU - Kaul,Dhananjay K, AU - Liu,Xiao-du, AU - Zhang,Xiaoqin, AU - Ma,Li, AU - Hsia,Carleton J C, AU - Nagel,Ronald L, Y1 - 2006/01/27/ PY - 2006/1/31/pubmed PY - 2006/8/2/medline PY - 2006/1/31/entrez SP - H167 EP - 75 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 291 IS - 1 N2 - In sickle cell anemia (SCA), inflammatory (i.e., intravascular sickling and transient vasoocclusive) events result in chronic endothelial activation. In addition to sickling behavior, sickle (SS) red blood cells exhibit abnormal interaction with the vascular endothelium, which is considered to have an important role in initiation of vasoocclusion. Upregulation of endothelial adhesion molecules caused by oxidants (and cytokines) may lead to increased SS red cell adhesion. We hypothesize that endothelial activation is indispensable in SS red cell adhesion to the endothelium and that antioxidants will have an inhibitory effect on this interaction. We examined the effect of selected antioxidants in ex vivo mesocecum vasculature, a well-established model that allows measurement of hemodynamic parameters and, by intravital microscopy, can allow quantification of adhesion. We tested antioxidant enzymes (SOD and catalase) and an intravascular SOD mimetic, polynitroxyl albumin (PNA), in the presence of platelet-activating factor (PAF); the latter causes endothelial oxidant generation and endothelial activation, which characterize SCA. In ex vivo preparations, PAF not only induced marked endothelial oxidant generation, it also enhanced SS red cell adhesion, resulting in frequent blockage of small-diameter venules. The adhesion, inversely related to venular diameter, and vasoocclusion were markedly inhibited by antioxidants, resulting in improved hemodynamics. PNA, the most effective antioxidant, also abolished SS red cell adhesion in non-PAF-activated preparations. Thus SS red cell adhesion and related vasoocclusion may be ameliorated by antioxidant therapy with a stable and long-acting molecule (e.g., PNA). SN - 0363-6135 UR - https://www.unboundmedicine.com/medline/citation/16443674/Inhibition_of_sickle_red_cell_adhesion_and_vasoocclusion_in_the_microcirculation_by_antioxidants_ L2 - http://www.physiology.org/doi/full/10.1152/ajpheart.01096.2005?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -