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Proteolytic Cleavage of the Red Blood Cell Glycocalyx in a Genetic Form of Hypertension

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Abstract

Recent evidence suggests that the spontaneously hypertensive rat (SHR) has an elevated level of proteases, including matrix metalloproteinases (MMPs), involved in cell membrane receptor cleavage. We hypothesize that SHR red blood cells (RBCs) may be subject to an enhanced glycocalyx cleavage compared to the RBCs of the normotensive Wistar-Kyoto (WKY) rats. By direct observation of RBC rouleaux, we found no significant difference in RBC aggregation for unseparated SHR and WKY RBCs. However, lighter SHR RBCs have a greater tendency to aggregate than WKY RBCs when separated by centrifugation. When SHR plasma was mixed with WKY RBCs, SHR plasma proteases cleaved the glycocalyx of WKY RBCs, a process that can be blocked by MMP inhibition. When treated with MMPs, WKY RBCs showed strong aggregation in dextran but not in fibrinogen, indicating that RBC membrane glycoproteins from the inner core of the glycocalyx were cleaved and that dextran was able to bind to the lipid portion of the RBC membrane. In contrast, treatment with amylases produced fibrinogen-induced aggregation with fibrinogen binding to the protein core. As a mechanism to remove old RBCs from the circulation, RBC adhesion to macrophages is reduced by MMP cleavage of the RBC glycocalyx.

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Acknowledgment

This research was supported by NHLBI grant HL 10881.

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No conflicts of interest are declared by the authors.

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Authors and Affiliations

  1. Department of Bioengineering, The Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, 92093-0412, USA

    Cécile Pot, Angela Y. Chen, Jessica N. Ha & Geert W. Schmid-Schönbein

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  1. Cécile Pot
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  2. Angela Y. Chen
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  3. Jessica N. Ha
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  4. Geert W. Schmid-Schönbein
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Correspondence to Geert W. Schmid-Schönbein.

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Associate Editors John Shyy and Yingxiao Wang oversaw the review of this article.

C. Pot and A. Y. Chen contributed equally to this work.

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Pot, C., Chen, A.Y., Ha, J.N. et al. Proteolytic Cleavage of the Red Blood Cell Glycocalyx in a Genetic Form of Hypertension. Cel. Mol. Bioeng. 4, 678–692 (2011). https://doi.org/10.1007/s12195-011-0180-0

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