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Atomic force microscopy as a tool to evaluate the risk of cardiovascular diseases in patients

Abstract

The availability of biomarkers to evaluate the risk of cardiovascular diseases is limited1. High fibrinogen levels have been identified as a relevant cardiovascular risk factor, but the biological mechanisms remain unclear2,3. Increased aggregation of erythrocytes (red blood cells) has been linked to high plasma fibrinogen concentration2,4. Here, we show, using atomic force microscopy, that the interaction between fibrinogen and erythrocytes is modified in chronic heart failure patients. Ischaemic patients showed increased fibrinogen–erythrocyte binding forces compared with non-ischaemic patients. Cell stiffness in both patient groups was also altered. A 12-month follow-up shows that patients with higher fibrinogen–erythrocyte binding forces initially were subsequently hospitalized more frequently. Our results show that atomic force microscopy can be a promising tool to identify patients with increased risk for cardiovascular diseases.

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Figure 1: AFM-based force spectroscopy set-up and its crude data.
Figure 2: AFM-based force spectroscopy data for the interactions between fibrinogen and erythrocytes from heart failure patients and healthy blood donors.
Figure 3: Changes in whole blood viscosity between ischaemic and non-ischaemic CHF patients and healthy donors.
Figure 4: Erythrocyte deformability measured at different shear stress values for all studied groups.
Figure 5: Hospitalization curve according to fibrinogen–erythrocyte (un)binding forces.

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Acknowledgements

This work was supported by Fundação para a Ciência e a Tecnologia – Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal) grants PTDC/QUI-BIQ/119509/2010 and PTDC/BBB-BMD/6307/2014, as well as fellowship SFRH/BD/84414/2012 to A.F.G. The authors thank T. Freitas (FMUL) for technical assistance.

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A.F.G. performed AFM experiments, analysed force spectroscopy data, performed the statistical analysis, wrote and edited the draft and prepared the manuscript for submission. F.A.C. analysed the force spectroscopy data, wrote the manuscript and edited successive drafts of the paper. I.M. performed some of the initial AFM experiments and analysed their data. L.S. collected all clinical data, performed some statistical analysis, contributed to relevant discussions and edited the draft. N.L. contributed to the discussion section and N.C.S. conceived the idea, designed and directed the AFM experiments, analysed the data, wrote the manuscript and edited successive drafts of the paper.

Corresponding authors

Correspondence to Filomena A. Carvalho or Nuno C. Santos.

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The authors declare no competing financial interests.

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Guedes, A., Carvalho, F., Malho, I. et al. Atomic force microscopy as a tool to evaluate the risk of cardiovascular diseases in patients. Nature Nanotech 11, 687–692 (2016). https://doi.org/10.1038/nnano.2016.52

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