Influence of HDL subfractions on erythrocyte aggregation in hypercholesterolemic men. PCVMETRA Group.

Abstract

Recent studies have suggested that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. We investigated the association between erythrocyte aggregation and components of lipoproteins in the blood of 60 normotensive, hypercholesterolemic men aged 45±8 years. The rheological parameters assessed were aggregation index (AI) and disaggregation shear rate threshold (yt) as determined by laser reflectometry, plasma fibrinogen, total serum protein, and hematocrit. The lipoprotein variables included total cholesterol, triglycerides, highdensity lipoprotein (HDL) cholesterol and its subfractions HDL 2 cholesterol and HDL3 cholesterol, apolipoprotein (apo) B, apoA-I, HDL particles containing apoA-I without apoA-II (LpA-I), and HDL particles containing both apoA-I and apoA-II (LpA-I/A-II). Covariables considered for possible confounding effects were age, body mass index, and smoking behavior. Fibrinogen, total serum protein, and both aggregation parameters (AI and yt) were elevated in this hypercholesterolemic population. Univariate analysis showed that both T he fluidity of blood plays an important role in the physiological behavior of the circulation, and its alteration might promote cardiovascular complications in situations associated with low-flow states. 1In this condition red blood cells (RBCs) aggregate due to the increase in the bridging force of high-molecularweight plasma proteins.12 Among these proteins, some are considered to be cardiovascular risk markers (eg, lipoproteins, fibrinogen) and are associated with increased plasma and whole-blood viscosity.313 Associations between rheology and components of lipoproteins in human blood are reported. Studies in patients with various forms of hyperlipoproteinemia show a concentration-dependent increase in plasma viscosity for lowdensity lipoprotein cholesterol (LDL-C) and chylomicrons and hence, for total triglycerides. 9 ' 10 These earlier studies are in line with the positive linear correlation of plasma viscosity with total cholesterol and apolipoprotein (apo) A-II and apoB observed in a recent study. 11Moreover, both blood viscosity 11 and erythrocyte aggregation 12 are negatively related to high-density lipoprotein cholesterol (HDL-C) concentration, which is known to be inversely correlated with coronary heart disease risk. 14 Furthermore, HDL may also be separated according to apolipoprotein composition, leading to at least two species of particles: LpA-I, which contains apoA-I without apoA-II, and LpA-I/A-II, which contains both apoA-I and apoA-II. 15 These heterogeneous HDL subfractions seem to have distinct metabolic roles, but the specific effect of one or another particle on the atherosclerotic process remains unclear. 1621 In the present study we investigated the relation of lipoprotein components, and especially HDL subfractions, to the aggregation and disaggregation of RBCs in a population of asymptomatic, hypercholesterolemic, normotriglyceridemic, normotensive subjects. Methods Selection of Su...

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

“…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 hypercholesterolemia, concentrations of LDL cholesterol, apolipoprotein B, and lipoprotein AI:AII correlated positively with aggregation parameters. 6,11 Cellular factors and erythrocyte aging have been less well studied.…”

“…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 hypercholesterolemia, concentrations of LDL cholesterol, apolipoprotein B, and lipoprotein AI:AII correlated positively with aggregation parameters.6,11 Cellular factors and erythrocyte aging have been less well studied.Membrane-bound sialic acid with carboxyl groups contributes to the majority of the negative surface charge of the erythrocyte.12,13 It has been shown that neuraminidase-treated erythrocytes show a decrease in surface-charge density and an increase in aggregation induced by dextran. 2,14,15 There have been few studies on the role of cell age in erythrocyte aggregation.…”

“…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.…”

Selective gene transfer to tumor cells by recombinant Newcastle Disease Virus via a bispecific fusion protein

“…Erythrocyte aggregation is one of the main determinants influencing blood circulation at low shear rates by increasing blood viscosity and inducing 'sludging' in the capillary (41). An increase in erythrocyte aggregation was found to be associated with cardiovascular risk factors such as hypertension (42) and hyperlipoproteinemia (43). A phase I trial of intravenous administration of the oncolytic NDV (PV701) showed that hypertension was observed in 5/7 patients.…”

High-Density Lipoproteins in Stroke

“…HDL 2 subfraction was reported to be inversely correlated with erythrocyte aggregation in hypercholesterolemic patients (Razavian et al 1994). A multiple regression analysis demonstrated that this association was independent of fibrinogen, the major determinant of erythrocyte aggregation.…”