Enzymatic hydrolysis of luminal coronary glycosidic structures uncovers their role in sensing coronary flow

Rubio-Gayosso, Iván; Barajas-Espinosa, Alma; Castillo-Hernández, Jesús; Ramiro-Diaz, Juan Manuel; Ceballos, Guillermo; Rubio, Rafael

doi:10.2741/1598

Cited by 9 publications

(33 citation statements)

References 32 publications

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“…Work from our laboratory and many others have shown that the perfusion of heparinase into blood vessels removes endothelial surface layer heparinic functional groups [10,11,31,13,39,40,42]. Heparinate, a branched oligosaccharide, is known to be lectinically bound to endothelial surface layer functional [40].…”

Section: Group 4: Effects Of Heparinase On the Concentration-vascularmentioning

confidence: 99%

“…To minimize the possibility of transendothelial diffusion, heparinase was administered repeatedly using a low concentration gradient and very short exposure times [8,11,13,31,44]. As described above, control concentration-response curves to bradykinin were obtained at 11 ml/ min (basal pressure 52.4 ± 2.6 mmHg) and at 16 ml/min (basal pressure 81.2 ± 6.8 mmHg).…”

Section: Groupmentioning

confidence: 99%

“…Heparinase treatment: Endogenous endothelial surface layer heparinate groups participate in diverse flow-induced responses [10,11,13,31], and these numerous groups can be exclusively and selectively hydrolyzed with intravascular heparinase [39][40][41][42][43]. To minimize the possibility of transendothelial diffusion, heparinase was administered repeatedly using a low concentration gradient and very short exposure times [8,11,13,31,44].…”

Section: Groupmentioning

confidence: 99%

“…Interestingly, the roles of individual endothelial surface sugars and lectins in flow-induced responses are function biased; a complexity that makes difficult to identify the exact "mechanosensor(s)" for each response [6,8,[10][11][12][13]15]. In contrast, in the case of a defined G-protein coupled receptor, the response triggered by its specific agonist identifies it as the structure of origin, the agonist-sensor [1,3,4,14].…”

Section: Introductionmentioning

confidence: 99%

“…Flow sensing properties likely reside in the luminal endothelial surface; constituted by the cell membrane and glycocalyx which is acted by flow [6][7][8][9][10][11][12][13]. We have shown that flowinduced responses require endothelial surface layer oligosaccharides and oligosaccharide-recognizing proteins, lectins because a) specific enzymatic hydrolysis of endogenous oligosaccharides or their binding to exogenous lectins exactly alter flow-induced responses and b) infusion of diverse exogenous oligosaccharides that bind to endothelial surface lectins alter the effects of flow [8,11,12].…”

Section: Introductionmentioning

confidence: 99%

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Flow enhances the agonist-induced responses of the bradykinin receptor (B2) because of its lectinic nature: Role of its oligosaccharide environment

Jiménez-Corona¹,

Espinosa‐Tanguma²,

Knabb³

et al. 2017

J Transl Sci

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Studies in perfused hearts show that flow-sensitive G-protein coupled receptors are lectinic suggesting that flow exerts its effects by modulating the interaction between endothelial surface layer oligosaccharides and lectinic transmembrane G-protein coupled receptors. To test this hypothesis guinea pig carotid arteries were perfused with Krebs-Henseleit at 11 or 16 ml/min. The effects of flow on the contraction induced by stimulating the bradykinin receptor were determined using the flow-induced changes of bradykinin concentration-vascular response curves. Flow effects on the bradykinin receptor were studied in four independent groups; in Groups 1 and 2 (controls) the endothelial surface layer glyosidic composition was not altered, in Group 3 an oligosaccharide polymer that lectinically and irreversibly binds to endothelial surface layer was infused, and in Group 4 endothelial surface layer heparinic were hydrolyzed. Results show that an increase in flow from 11 to 16 ml/min shifted the vascular response curve of bradykinin upward and to the left. Similar results were obtained with endothelial surface layer oligosaccharide polymer binding and heparinic removal but elevation of flow from 11 to 16 ml/min had no effect. Thus, the flow dependence of the lectinic bradykinin receptor depends on its ability to interact with the oligosaccharide environment and heparinic groups.

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Section: Group 4: Effects Of Heparinase On the Concentration-vascularmentioning

confidence: 99%

Section: Groupmentioning

confidence: 99%

Section: Groupmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Flow enhances the agonist-induced responses of the bradykinin receptor (B2) because of its lectinic nature: Role of its oligosaccharide environment

Jiménez-Corona¹,

Espinosa‐Tanguma²,

Knabb³

et al. 2017

J Transl Sci

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G protein-coupled receptors mediate coronary flow- and agonist-induced responses via lectin-oligosaccharide interactions

Perez-Aguilar

Torres-Tirado

Martell-Gallegos

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Blood flow acts parallel to the coronary luminal endothelial surface layer (LESL) and modulates multiple parenchymal functions via the release of paracrine agents. Evidence indicates that the LESL may be a flow-sensing organelle and that perhaps through flow-induced lectin (L)·oligosaccharide (O) complex formation (L·O) participates in this process. LESL integrins and selectins are both lectinic and flow sensitive, but the L properties of flow-sensitive G protein-coupled receptors (GPCRs) are unknown. Therefore, we investigated the presence of L in the LESL and hypothesized that if flow-sensitive GPCRs are L, flow and O will determine their response to receptor activation. The LESL protein fraction isolated from guinea pig hearts was passed through an affinity chromatography column made of three sugars, mannose, galactose, and N-acetylglucosamine, and the lectinic fraction was eluted. Immune dot blot was used to identify L proteins in the LESL fraction. Our results indicate the following. 1) Two-dimensional SDS-PAGE (2D-SDS-PAGE) of the LESL lectinic fraction revealed at least 167 Ls. 2) Among these Ls, we identified three selectins and the GPCRs: angiotensin II, bradykinin (B2-R), adenosine A1 and A2, prolactin, endothelin, α1-adrenergic (α1A-R), thromboxane A2, β1-adrenergic, β3-adrenergic, and insulin receptors; the first six GPCRs are known to be flow sensitive. 3) The amplitude of receptor-induced vascular responses by α1A-R and B2-R activation (phenylephrine or bradykinin, respectively) was a function of flow and O (hyaluronidate). Our results support a novel mechanism of GPCR-mediated responses to flow via L·O interaction.

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

Ramiro-Diaz

Barajas-Espinosa

Chi‐Ahumada

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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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 [-4GlcUAbeta1-3GlcNAcbeta1-](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 beta-ENaC channel. Some of these lectins could participate in flow sensing and in GlcNac-Pol-induced 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.

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Enzymatic hydrolysis of luminal coronary glycosidic structures uncovers their role in sensing coronary flow

Cited by 9 publications

References 32 publications

Flow enhances the agonist-induced responses of the bradykinin receptor (B2) because of its lectinic nature: Role of its oligosaccharide environment

Flow enhances the agonist-induced responses of the bradykinin receptor (B2) because of its lectinic nature: Role of its oligosaccharide environment

G protein-coupled receptors mediate coronary flow- and agonist-induced responses via lectin-oligosaccharide interactions

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

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