Fibrinogen-erythrocyte binding and hemorheology measurements in the assessment of essential arterial hypertension patients.

Some studies have reported a positive association between plasma fibrinogen levels, erythrocyte aggregation and essential arterial hypertension (EAH). The aim of this study was to understand how the interaction between fibrinogen and its erythrocyte membrane receptor is altered in EAH. EAH patients (n = 31) and healthy blood donors (n = 65) were enrolled in the study. EAH patients were therapeutically controlled for the disease, presenting a systolic blood pressure between 108 and 180 mmHg and a diastolic blood pressure between 66 and 123 mmHg. Clinical evaluation included blood pressure monitoring, electrocardiography, echocardiography and blood cell count. The hemorheological parameters were also analyzed. Fibrinogen-erythrocyte binding force and frequency were evaluated quantitatively, at the single-molecule level, using atomic force microscopy (AFM). Changes in erythrocyte elasticity were also evaluated. Force spectroscopy data showed that the average fibrinogen-erythrocyte binding forces increase from 40.4 ± 3.0 pN in healthy donors to 73.8 ± 8.1 pN in patients with EAH, despite a lower binding frequency for patients compared to the control group (7.9 ± 1.6% vs. 27.6 ± 4.2%, respectively). Elasticity studies revealed an increase of erythrocyte stiffness in the patients. The stronger fibrinogen binding to erythrocytes from EAH patients and alteration in cell elasticity may lead to changes in the whole blood flow. The patients' altered hemorheological parameters may also contribute to these blood flow perturbations. The transient bridging of two erythrocytes, by the simultaneous binding of fibrinogen to both of them, promoting erythrocyte aggregation, could represent an important cardiovascular risk factor.

Essential arterial hypertension patients present higher cell adhesion forces, contributing to fibrinogen-dependent cardiovascular risk.

The increase of erythrocyte aggregation by high fibrinogen levels may be an indicator of cardiovascular risk. γ' fibrinogen variant has been considered as a possible player in enhancing aggregation. Here, we assessed, at the single-cell level, the influence of fibrinogen on erythrocyte aggregation in essential arterial hypertension. We also aimed at understanding how γ' fibrinogen is altered in this disease. Using atomic force microscopy (AFM), we show that the work and force necessary for erythrocyte-erythrocyte detachment is higher for patients than for healthy donors, with these parameters further increasing in both groups when higher fibrinogen concentrations are present. This can be associated with changes in blood flow, due to transient bridging of two erythrocytes by fibrinogen, representing an important cardiovascular risk factor. γ' fibrinogen can influence the increased risk in essential arterial hypertension, as we demonstrate that its levels are significantly increased in these patients' blood. Nevertheless, this cannot be the only cause for the changes observed in the AFM data.