Luminal endothelial lectins with affinity for N-acetylglucosamine determine flow-induced cardiac and vascular paracrine-dependent responses

Juan Ramiro-Diaz, Alma Barajas-Espinosa, Erika Chi-Ahumada, Sandra Perez-Aguilar, David Torres-Tirado, Jesus Castillo-Hernandez, Maureen Knabb, Ana Barba De La Rosa, Rafael Rubio

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Coronary blood flow applied to the endothelial lumen modulates parenchymal functions via paracrine effectors, but the mechanism of flow sensation is unknown. We and others have demonstrated that coronary endothelial luminal membrane (CELM) oligosaccharides and lectins are involved in flow detection, and we proposed that cardiac effects of coronary flow result from a reversible flow-modulated lectin-oligosaccharide interaction. Recently, glycosylated and amiloride-sensitive Na+/Ca++ channels (ENaCs) have been proposed to be involved in the flow-induced endothelial responses. Because N-acetylglucosamine (GlcNac) is one of the main components of glycocalyx oligosaccharides (i.e., hyaluronan [-4GlcUAβ1-3GlcNAcβ1-] n), the aim of this article is to isolate and define CELM GlcNac-binding lectins and determine their role in cardiac and vascular flow-induced effects. For this purpose, we synthesized a 460-kDa GlcNac polymer (GlcNac-Pol) with high affinity toward GlcNac-recognizing lectins. In the heart, intracoronary administration of GlcNac-Pol upon binding to CELM diminishes the flow-dependent positive inotropic and dromotropic effects. Furthermore, GlcNac-Pol was used as an affinity probe to isolate CELM GlcNac-Pol-recognizing lectins and at least 35 individual lectinic peptides were identified, one of them the β-ENaC channel. Some of these lectins could participate in flow sensing and in GlcNac-Polinduced effects. We also adopted a flow-responsive and well-accepted model of endothelial-parenchymal paracrine interaction: isolated blood vessels perfused at controlled flow rates. We established that flow-induced vasodilatation (FIV) is blocked by endothelial luminal membrane (ELM) bound GlcNac-Pol, nitro-L-arginine methyl ester and indomethacin, amiloride, and hyaluronidase. The effect of hyaluronidase was reversed by infusion of soluble hyaluronan. These results indicate that GlcNac-Pol inhibits FIV by competing and displacing intrinsic hyaluronan bound to a lectinic structure such as the amiloride-sensitive ENaC. Nitric oxide and prostaglandins are the putative paracrine mediators of FIV.

Original languageEnglish (US)
Pages (from-to)H743-H751
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number3
DOIs
StatePublished - Sep 2010
Externally publishedYes

Keywords

  • Endothelium
  • Epithelial Na channel
  • Flow-induced paracrine mechanisms
  • Nitric oxide
  • Prostaglandins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Ramiro-Diaz, J., Barajas-Espinosa, A., Chi-Ahumada, E., Perez-Aguilar, S., Torres-Tirado, D., Castillo-Hernandez, J., Knabb, M., De La Rosa, A. B., & Rubio, R. (2010). Luminal endothelial lectins with affinity for N-acetylglucosamine determine flow-induced cardiac and vascular paracrine-dependent responses. American Journal of Physiology - Heart and Circulatory Physiology, 299(3), H743-H751. https://doi.org/10.1152/ajpheart.00790.2009