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

Dhananjay K. Kaul, Xiao Du Liu, Xiaoqin Zhang, Li Ma, Carleton J.C. Hsia, Ronald L. Nagel

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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).

Original languageEnglish
Pages (from-to)H167-H175
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number1
DOIs
StatePublished - 2006

Keywords

  • Endothelium
  • Inflammation
  • Platelet-activating factor
  • Polynitroxyl albumin
  • Sickle cell disease

Fingerprint

Dive into the research topics of 'Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation by antioxidants'. Together they form a unique fingerprint.

Cite this