Inserm Unit 970 – Paris Cardiovascular Research Center
A new study published in the journal Blood shows that red blood cells can turn against blood vessels by releasing aggressive fragments that contribute to the development of cardiovascular diseases.
There are approximately 5 million red blood cells in every microlitre of blood. Their stock is constantly renewed, and each one is discreetly removed every three months. But abnormal red blood cells persist in the bloodstream in some diseases. They ultimately rupture and release their contents, a process referred to as intravascular haemolysis.
Does the red blood cell disappear then? Not quite…
Researchers led by Olivier Blanc-Brude, a CNRS (French National Centre for Scientific Research) research fellow at the Inserm Paris Cardiovascular Center and Paris Descartes University, have just shown that at the exact moment of haemolysis, the red blood cells do not disappear: they actually release a large number of fragments, known as microparticles. And these fragments are not harmless. These observations were made using red blood cells from patients with sickle cell disease, the most common genetic disorder in France. Their rigidity leads to a considerable degree of haemolysis, which is therefore easier to study.
Red blood cells contain haemoglobin, the protein that carries blood gases and enables us to breathe. As a result, the red blood cell fragments also contain haemoglobin, but in a degraded and toxic form: the iron previously contained in the haemoglobin becomes exposed on the surface of these thousands of red blood cell microparticles.
It is this feature that makes the microparticles dangerous.
Effectively, the red blood cell particles act as carriers, and deposit the toxic substances on the cells lining the blood vessels. This transfer of haem and iron from the red blood cells to the vascular lining interferes with dilation, limiting the blood supply to the tissues that need it. This also leads to oxidative stress and promotes obstruction of the blood vessels.
These innovative results make it possible to anticipate new therapeutic possibilities for preventing and treating vaso-occlusive crises, as well as for preventing some more common cardiovascular diseases.
These new therapies could target various components of the red blood cell microparticles, e.g. membrane components, such as phosphatidylserine, or free haem. Haemopexin is a molecule naturally found in the bloodstream, and which has the role of binding to free haem to eliminate it. It might represent a therapeutic opportunity, i.e. a haemopexin supplement might help to neutralise free haem carried by red blood cell microparticles.
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Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease Stéphane M. Camus1, João A. De Moraes1, Philippe Bonnin2, Paul Abbyad3, Sylvain Le Jeune4, François Lionnet5, Laurent Loufrani6, Linda Grimaud6, Jean-Christophe Lambry3, Dominique Charue1, Laurent Kiger7, Jean-Marie Renard1, Claire Larroque8, Hervé Le Clésiau8, Alain Tedgui1, Patrick Bruneval1, Christina Barja-Fidalgo9, Antigoni Alexandrou3, Pierre-Louis Tharaux1, Chantal M. Boulanger1, and Olivier P. Blanc-Brude1 1 Paris Center for Cardiovascular Research, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche-970, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, and Université Paris Descartes, Sorbonne Paris Cité, Paris, France; 2 Institut National de la Santé et de la Recherche Médicale U965, Université Paris Diderot, Sorbonne Paris Cité, and Physiologie Clinique-Explorations-Fonctionnelles, Hôpital Lariboisière, AP-HP, Paris, France; 3 Optics and Biosciences Laboratory, Institut National de la Santé et de la Recherche Médicale U696, and Ecole Polytechnique, Palaiseau, France; 4 Service de Médecine Interne et Hypertension Artérielle, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Bobigny, France; 5 Service de Médecine Interne, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France; 6 Department of Integrated Neurovascular Biology, Institut National de la Santé et de la Recherche Médicale U771, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6214, and Université d’Angers, Angers, France; 7 Institut National de la Santé et de la Recherche Médicale U955, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil and Universités Paris VI and XI, Paris, France; 8 Centre d’Examens de Santé, Caisse Primaire d’Assurance Maladie Seine St Denis, Bobigny, France; and 9 Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil Blood, 31 March 2015