Sialic acids rather than glycosaminoglycans affect normal and sickle red blood cell rheology by binding to four major sites on fibrinogen

Gondelaud, Frank; Connes, Philippe; Nader, Élie; Renoux, Céline; Fort, Romain; Gauthier, Alexandra; Joly, Philippe; Ricard‐Blum, Sylvie

doi:10.1002/ajh.25718

Cited by 9 publications

(7 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2017; Gondelaud et al . 2020) could be involved. At higher shear rates, blood viscosity was higher in the most severe group compared to highlanders without CMS but no significant difference in blood viscosity was noted between the mild CMS group and healthy highlanders despite the fact that haematocrit and haemoglobin concentration were higher in the two groups with CMS.…”

Section: Discussionmentioning

confidence: 99%

“…RBC aggregation was lower in highlanders with moderate-to-severe CMS compared to individuals without CMS, which could have partly offset the effects of the increased haematocrit and haemoglobin levels on blood viscosity measured at the lowest shear rate. The reasons for the lower RBC aggregation found in individuals with moderate-to-severe J Physiol 598.18 CMS are unknown and need to be explored further but several mechanisms such as lower plasma fibrinogen, thrombospondin, von Willebrand factor concentrations (plasma factors) or difference in RBC membrane sialic contents (cellular factors) Nader et al 2017;Gondelaud et al 2020) could be involved. At higher shear rates, blood viscosity was higher in the most severe group compared to highlanders without CMS but no significant difference in blood viscosity was noted between the mild CMS group and healthy highlanders despite the fact that haematocrit and haemoglobin concentration were higher in the two groups with CMS.…”

Section: Haemorheologymentioning

confidence: 99%

“…CMS are unknown and need to be explored further but several mechanisms such as lower plasma fibrinogen, thrombospondin, von Willebrand factor concentrations (plasma factors) or difference in RBC membrane sialic contents (cellular factors) Nader et al 2017;Gondelaud et al 2020) could be involved. At higher shear rates, blood viscosity was higher in the most severe group compared to highlanders without CMS but no significant difference in blood viscosity was noted between the mild CMS group and healthy highlanders despite the fact that haematocrit and haemoglobin concentration were higher in the two groups with CMS.…”

Section: Haemorheologymentioning

confidence: 99%

See 2 more Smart Citations

Blood viscosity and its determinants in the highest city in the world

Stauffer

Loyrion

Hancco

et al. 2020

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Key points Highlanders develop unique adaptative mechanisms to chronic hypoxic exposure, including substantial haemoglobin and haematocrit increases. However, a significant proportion of populations living permanently at high altitude develop maladaptive features known as chronic mountain sickness (CMS). This study aimed to assess the effects of permanent life at high altitude on clinical and haemorheological parameters (blood viscosity and red blood cell aggregation) and to compare clinical and haemorheological parameters of dwellers from the highest city in the world according to CMS severity. Blood viscosity increased with altitude, together with haemoglobin concentration and haematocrit. At 5100 m, highlanders with moderate‐to‐severe CMS had higher blood viscosity mainly at high shear rate and even at corrected haematocrit (40%), with a lower red blood cell aggregation. Blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit. Abstract Chronic mountain sickness (CMS) is a condition characterised by excessive erythrocytosis (EE). While EE is thought to increase blood viscosity and subsequently to trigger CMS symptoms, the exact relationship between blood viscosity and CMS symptoms remains incompletely understood. We assessed the effect of living at high altitude on haemoglobin, haematocrit and haemorheological parameters (blood viscosity and red blood cell aggregation), and investigated their relationship with CMS in highlanders living in the highest city in the world (La Rinconada, Peru, 5100 m). Ninety‐three men participated in this study: 10 Caucasian lowlanders, 13 Andean highlanders living at 3800 m and 70 Andean highlanders living at 5100 m (35 asymptomatic, CMS score ≤5; 15 with mild CMS, CMS score between 6 and 10; 20 with moderate‐to‐severe CMS, CMS score >10). Blood viscosity was measured at native and corrected haematocrit (40%). Haemoglobin concentration and haematocrit increased with the altitude of residency. Blood viscosity also increased with altitude (at 45 s−1: 6.7 ± 0.9 mPa s at sea level, 14.0 ± 2.0 mPa s at 3800 m and 27.1 ± 8.8 mPa s at 5100 m; P < 0.001). At 5100 m, blood viscosity at corrected haematocrit was higher in highlanders with moderate‐to‐severe CMS (at 45 s−1: 18.9 ± 10.7 mPa s) than in highlanders without CMS (10.2 ± 5.9 mPa s) or with mild CMS (12.1 ± 6.1 mPa s) (P < 0.05). In conclusion, blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Haemorheologymentioning

confidence: 99%

Section: Haemorheologymentioning

confidence: 99%

See 1 more Smart Citation

Blood viscosity and its determinants in the highest city in the world

Stauffer

Loyrion

Hancco

et al. 2020

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous research indicates that increased PS exposure at the RBC membrane level could be involved in enhanced RBC adhesiveness to endothelial cells, but it does not appear to play a role in RBC aggregation [ 28 , 29 ]. However, RBC aging is accompanied by a decrease in sialic acid content [ 30 ], which could have resulted in increased RBC aggregability [ 31 ] and thus aggregation, in the MCC runners. Nevertheless, CD235-A expression, the main sialoglycoprotein of the RBC membrane, did not change in MCC runners.…”

Section: Discussionmentioning

confidence: 99%

Impact of Trail Running Races on Blood Viscosity and Its Determinants: Effects of Distance

Robert

Stauffer

Nader

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Blood rheology is a key determinant of tissue perfusion at rest and during exercise. The present study investigated the effects of race distance on hematological, blood rheological, and red blood cell (RBC) senescence parameters. Eleven runners participated in the Martigny–Combes à Chamonix 40 km race (MCC, elevation gain: 2300 m) and 12 others in the Ultra-Trail du Mont Blanc (UTMB, 171 km, elevation gain: 10,000 m). Blood samples were collected before and after the races. After the UTMB, the percentage of RBC phosphatidylserine (PS) exposure was not affected while RBC CD235a levels decreased and RBC-derived microparticles increased. In contrast, after the MCC, RBC PS exposure increased, while RBC CD235a and RBC-derived microparticles levels were not affected. The free hemoglobin and hemolysis rate did not change during the races. RBC aggregation and blood viscosity at moderate shear rates increased after the MCC. RBC deformability, blood viscosity at a high shear rate, and hematocrit decreased after the UTMB but not after the MCC. Our results indicate that blood rheology behavior is different between a 40 km and a 171 km mountain race. The low blood viscosity after the ultra-marathon might facilitate blood flow to the muscles and optimize aerobic performance.

show abstract

“…Conditioned media from 293T cells stably expressing FLAG-tagged fl-SNED1 and the N-terminal fragment of SNED1 were incubated with PNGase F as previously described (58), or with heparinase III and chondroitinase ABC (2 mU per 40 μL of CM) as previously described (59). Proteins were separated by SDS-PAGE, and transferred onto nitrocellulose membranes.…”

Section: Analysis Of Sned1 Post-translational Modifications By Sds-pamentioning

confidence: 99%

Computational and experimental characterization of the novel ECM glycoprotein SNED1 and prediction of its interactome

Vallet

Davis

Barqué

et al. 2020

Preprint

View full text Add to dashboard Cite

The extracellular matrix (ECM) protein SNED1 has been shown to promote breast cancer metastasis and control neural crest cell-specific craniofacial development, but the cellular and molecular mechanisms by which it does so remain unknown. ECM proteins exert their functions by binding to cell surface receptors, sequestering growth factors, and interacting with other ECM proteins, actions that can be predicted using knowledge of protein’s sequence, structure and post-translational modifications. Here, we combined in-silico and in-vitro approaches to characterize the physico-chemical properties of SNED1 and infer its putative functions. To do so, we established a mammalian cell system to produce and purify SNED1 and its N-terminal fragment, which contains a NIDO domain. We have determined experimentally SNED1’s potential to be glycosylated, phosphorylated, and incorporated into insoluble ECM produced by cells. In addition, we used biophysical and computational methods to determine the secondary and tertiary structures of SNED1 and its N-terminal fragment. The tentative ab-initio model we built of SNED1 suggests that it is an elongated protein presumably able to bind multiple partners. Using computational predictions, we identified 114 proteins as putative SNED1 interactors. Pathway analysis of the newly-predicted SNED1 interactome further revealed that binding partners of SNED1 contribute to signaling through cell surface receptors, such as integrins, and participate in the regulation of ECM organization and developmental processes. Altogether, we provide a wealth of information on an understudied yet important ECM protein with the potential to decipher its functions in physiology and diseases.

show abstract

Sialic acids rather than glycosaminoglycans affect normal and sickle red blood cell rheology by binding to four major sites on fibrinogen

Cited by 9 publications

References 7 publications

Blood viscosity and its determinants in the highest city in the world

Blood viscosity and its determinants in the highest city in the world

Impact of Trail Running Races on Blood Viscosity and Its Determinants: Effects of Distance

Computational and experimental characterization of the novel ECM glycoprotein SNED1 and prediction of its interactome

Contact Info

Product

Resources

About