Erythrocyte Disaggregation Shear Stress, Sialic Acid, and Cell Aging in Humans

Abstract

Abstract-Erythrocyte aggregation, which plays an important role in the physiological behavior of blood fluidity, was found to be enhanced in hypertension and hypercholesterolemia. While the role of macromolecule bridging force has been widely described, cellular factors related to membrane sialic acid content, which might contribute to the negative charge of cell surface causing the repulsion of erythrocytes, have been less studied. Cell age-dependent changes in membrane sialic acid content (in micromoles per gram of integral membrane protein) were investigated in 24 normotensive and 24 hypertensive matched subjects, each divided into 2 identical subgroups according to a cutoff of 6.2 mmol/L serum cholesterol. A progressive and significant (PϽ0.001) decrease in membrane sialic acid content associated with an increase (PϽ0.001) of disaggregation shear rate threshold (laser reflectometry in the presence of dextran) were observed with increased erythrocyte density (erythrocytes fractionated by density using ultracentrifugation) in both normotensive and hypertensive groups regardless of the cholesterol level. However, disaggregation shear rate threshold was significantly higher and sialic acid content was lower (PϽ0.001) in both hypertensive and normotensive subjects with hypercholesterolemia compared with either normotensive or hypertensive subjects with low cholesterol, respectively. A high membrane sialic acid content variance, beginning in the younger erythrocytes, was due mainly to triglyceride and LDL cholesterol levels (R 2 ϭ0.49 for low, R 2 ϭ0.43 for middle, and R 2 ϭ0.54 for high densities, ie, young, mean, and senescent erythrocytes, respectively). We conclude that an early decrease in erythrocyte sialic acid content may influence the rheological properties of blood by increasing the adhesive energy of erythrocyte aggregates. (Hypertension. 1998;32:324-330.) Key Words: erythrocyte aggregation Ⅲ rheology Ⅲ sialic acid Ⅲ hypertension, essential Ⅲ hypercholesterolemia E rythrocyte aggregation is one of the main determinants influencing blood circulation at low shear rates by increasing blood viscosity and inducing "sludging" in the capillary.1 Aggregation of red blood cells is a reversible process that occurs when the bridging force due to the adsorption of macromolecules onto adjacent cell surfaces exceeds the disaggregation forces caused by electrostatic repulsion, membrane strain, and mechanical shearing. [1][2][3] An increase in erythrocyte aggregation was found to be associated with cardiovascular risk factors such as hypertension, 4 hyperlipoproteinemia, 5,6 and smoking 7 and in clinical situations such as myocardial ischemia, 8 thromboembolic states, 9 and retinal venous occlusion. 10 In general, most studies have focused on the ability of plasma proteins and various polymers to induce erythrocyte aggregation. We showed that in hypertension and hypercholesterolemia the increase in erythrocyte aggregation could be attributed to an increase in the concentration of plasma fibrinogen. 4,6 In addition, in ...

Glycophorin-C sialylation regulates Lu/BCAM adhesive capacity during erythrocyte aging

“…During erythrocyte lifespan, sialic acid content is gradually lost. [23][24][25] Indeed, the dense erythrocytes we isolated that adhered better to laminin-a5 contained significantly less a2,3-linked sialic acid ( Figure 1C). We tested whether red cell membrane sialic acid loss would induce Lu/BCAM activation.…”

Sialic acid in cardiovascular diseases

“…It is hypothesized that by removing sialic acid residues and thus eliminating forces of mutual repulsion of similarly charged membranes, plasma sialidase activity agglomerates the red cell mass (79). An early decrease in erythrocyte sialic acid content has been suggested to influence the rheological properties of blood by increasing the adhesive energy of erythrocytes aggregates (80).…”

Erythrocyte membrane bound and plasma sialic acid during aging

“…The involvement of sialic acid in red cell senescence has long been investigated. A decrease in membrane sialic acid has been reported in red cells during its life span of 120 days (Hadengue et al 1998), and its role as a determinant of the erythrocyte lifespan was described in several reports (Durocher et al 1975;Brovelli et al 1977). It has been reported that human 'ghost' membranes are able to release, by an autolytic process, a glycopeptide in which 30-60% of total membrane sialic acid is present.…”