atherosclerosis; thrombosis; intercellular communication; connexins; pannexins; gap junctions; endothelium; platelets
Molica Filippo, Meens Merlijn J., Pelli Graziano, Hautefort Aurélie, Emre Yalin, Imhof Beat A., Fontana Pierre, Scemes Eliana, Morel Sandrine, Kwak Brenda R. (2019), Selective inhibition of Panx1 channels decreases hemostasis and thrombosis in vivo, in Thrombosis Research
, 183, 56-62.
Nowak-Sliwinska Patrycja, Alitalo Kari, Allen Elizabeth, Anisimov Andrey, Aplin Alfred C., Auerbach Robert, Augustin Hellmut G., Bates David O., van Beijnum Judy R., Bender R. Hugh F., Bergers Gabriele, Bikfalvi Andreas, Bischoff Joyce, Böck Barbara C., Brooks Peter C., Bussolino Federico, Cakir Bertan, Carmeliet Peter, Castranova Daniel, Cimpean Anca M., Cleaver Ondine, Coukos George, Davis George E., De Palma Michele, et al. (2018), Consensus guidelines for the use and interpretation of angiogenesis assays, in Angiogenesis
, 21(3), 425-532.
Molica Filippo, Figueroa Xavier, Kwak Brenda, Isakson Brant, Gibbins Jonathan (2018), Connexins and Pannexins in Vascular Function and Disease, in International Journal of Molecular Sciences
, 19(6), 1663-1663.
Ruez Richard, Dubrot Juan, Zoso Alice, Bacchetta Marc, Molica Filippo, Hugues Stéphanie, Kwak Brenda R., Chanson Marc (2018), Dendritic Cell Migration Toward CCL21 Gradient Requires Functional Cx43, in Frontiers in Physiology
, 9, 288.
Carballo Sebastian, Pfenniger Anna, Carballo David, Garin Nicolas, James Richard, Mach François, Shah Dipen, Kwak Brenda (2018), Differential Association of Cx37 and Cx40 Genetic Variants in Atrial Fibrillation with and without Underlying Structural Heart Disease, in International Journal of Molecular Sciences
, 19(1), 295-295.
Meens Merlijn J, Kutkut Issa, Rochemont Viviane, Dubrot Juan, Kaladji Fouad R, Sabine Amélie, Lyons Oliver, Hendrikx Stefanie, Bernier-Latmani Jeremiah, Kiefer Friedemann, Smith Alberto, Hugues Stéphanie, Petrova Tatiana V, Kwak Brenda R (2017), Cx47 fine-tunes the handling of serum lipids but is dispensable for lymphatic vascular function., in PloS one
, 12(7), 0181476-0181476.
Stierlin Florian B, Molica Filippo, Reny Jean-Luc, Kwak Brenda R, Fontana Pierre (2017), Pannexin1 Single Nucleotide Polymorphism and Platelet Reactivity in a Cohort of Cardiovascular Patients., in Cell communication & adhesion
, 23(1), 11-15.
Molica Filippo, Meens Merlijn J., Dubrot Juan, Ehrlich Avigail, Roth Christel L., Morel Sandrine, Pelli Graziano, Vinet Laurent, Braunersreuther Vincent, Ratib Osman, Chanson Marc, Hugues Stephanie, Scemes Eliana, Kwak Brenda R. (2017), Pannexin1 links lymphatic function to lipid metabolism and atherosclerosis, in Scientific Reports
, 7(1), 13706-13706.
Ribeiro-Rodrigues Teresa M., Martins-Marques Tânia, Morel Sandrine, Kwak Brenda R., Girão Henrique (2017), Role of connexin 43 in different forms of intercellular communication – gap junctions, extracellular vesicles and tunnelling nanotubes, in Journal of Cell Science
, 130(21), 3619-3630.
Leybaert Luc, Lampe Paul D, Dhein Stefan, Kwak Brenda R, Ferdinandy Peter, Beyer Eric C, Laird Dale W, Naus Christian C, Green Colin R, Schulz Rainer (2017), Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications., in Pharmacological reviews
, 69(4), 396-478.
Denis Jean-Francois, Scheckenbach K E Ludwig, Pfenniger Anna, Meens Merlijn J, Krams Rob, Miquerol Lucile, Taffet Steven, Chanson Marc, Delmar Mario, Kwak Brenda R (2017), Connexin40 controls endothelial activation by dampening NFκB activation., in Oncotarget
, 8(31), 50972-50986.
Molica Filippo, Stierlin Florian, Fontana Pierre, Kwak Brenda (2017), Pannexin- and Connexin-Mediated Intercellular Communication in Platelet Function, in International Journal of Molecular Sciences
, 18(4), 850-850.
Molica Filippo, Nolli Séverine, Fontana Pierre, Kwak Brenda Renata (2017), Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor Brilliant Blue FCF on Collagen-induced Aggregation, in Journal of Visualized Experiments
, (122), e55525.
Morbiducci Umberto, Kok Annette M, Kwak Brenda R, Stone Peter H, Steinman David A, Wentzel Jolanda J (2016), Atherosclerosis at arterial bifurcations: evidence for the role of haemodynamics and geometry., in Thrombosis and haemostasis
, 115(3), 484-92.
Kauffenstein Gilles, Tamareille Sophie, Prunier Fabrice, Roy Charlotte, Ayer Audrey, Toutain Bertrand, Billaud Marie, Isakson Brant E, Grimaud Linda, Loufrani Laurent, Rousseau Pascal, Abraham Pierre, Procaccio Vincent, Monyer Hannah, de Wit Cor, Boeynaems Jean-Marie, Robaye Bernard, Kwak Brenda R, Henrion Daniel (2016), Central Role of P2Y6 UDP Receptor in Arteriolar Myogenic Tone., in Arteriosclerosis, thrombosis, and vascular biology
, 36(8), 1598-606.
Willebrords Joost, Crespo Yanguas Sara, Maes Michaël, Decrock Elke, Wang Nan, Leybaert Luc, Kwak Brenda R, Green Colin R, Cogliati Bruno, Vinken Mathieu (2016), Connexins and their channels in inflammation., in Critical reviews in biochemistry and molecular biology
Morel Sandrine, Christoffersen Christina, Axelsen Lene N, Montecucco Fabrizio, Rochemont Viviane, Frias Miguel A, Mach Francois, James Richard W, Naus Christian C, Chanson Marc, Lampe Paul D, Nielsen Morten S, Nielsen Lars B, Kwak Brenda R (2016), Sphingosine-1-phosphate reduces ischaemia-reperfusion injury by phosphorylating the gap junction protein Connexin43., in Cardiovascular research
, 109(3), 385-96.
Hoefer Imo E, Steffens Sabine, Ala-Korpela Mika, Bäck Magnus, Badimon Lina, Bochaton-Piallat Marie-Luce, Boulanger Chantal M, Caligiuri Giuseppina, Dimmeler Stefanie, Egido Jesus, Evans Paul C, Guzik Tomasz, Kwak Brenda R, Landmesser Ulf, Mayr Manuel, Monaco Claudia, Pasterkamp Gerard, Tuñón Jose, Weber Christian, Weber Christian (2015), Novel methodologies for biomarker discovery in atherosclerosis., in European heart journal
, 36(39), 2635-42.
Pfenniger A, Meens M J, Pedrigi R M, Foglia B, Sutter E, Pelli G, Rochemont V, Petrova T V, Krams R, Kwak B R (2015), Shear stress-induced atherosclerotic plaque composition in ApoE(-/-) mice is modulated by connexin37., in Atherosclerosis
, 243(1), 1-10.
Atherosclerosis, the leading cause of mortality worldwide, is an inflammatory disease of large and medium-sized arteries. The disease involves the formation of plaques in the intima of arteries that are characterized by a dysfunctional endothelium, recruitment of leukocytes, lipid accumulation, cell death and fibrosis. Atherosclerotic plaques develop predominantly at locations where blood flow is disturbed, i.e. arterial bifurcations and branch points. The most severe clinical events follow the rupture of an atherosclerotic lesion, which exposes the pro-thrombotic material in the plaque to the blood resulting in thrombus formation and occlusion of the artery at the disruption site.Connexin-mediated intercellular communication through both hemichannels and gap junction channels plays an important role in atherogenesis and thrombosis. Using mouse models for atherosclerosis, we have previously shown that Cx43 has an overall atherogenic effect, and that reducing Cx43 is beneficial by both reducing plaque burden as well as inducing a more stable lesion phenotype. In contrast, Cx40 protects against atherosclerosis in mice by synchronizing endothelial anti-inflammatory signaling thus inhibiting leukocyte recruitment to the plaques. Furthermore, Cx37 hemichannels control the initiation of atherosclerosis in mice by inhibiting autocrine ATP-dependent regulation of monocyte adhesion. In addition, arterial blood flow patterns regulate Cx37 expression thereby inducing the formation of communication compartments in the endothelium. Finally, the formation of Cx37 gap junction channels between platelets inhibits aggregation and limits thrombus growth in mice. Little is known however on the role Pannexin1 (Panx1), a structurally-related protein forming ATP release channels in the endothelium, leukocytes and platelets, in atherosclerosis development, plaque stability and thrombosis. In addition, the potential role of connexins in the creation of endothelial communication compartments that may contribute to localization of atherosclerotic disease has been only partly resolved.Preliminary experiments revealed altered atherogenesis in mice with deletion of Panx1. Moreover, chemical blockade of Panx1 in human platelets reduced aggregation in vitro. The first goal of the present project is to examine in detail the cellular/molecular mechanism by which Panx1 affects atherogenesis in mice. Secondly, we intend to determine whether Panx1 in platelets may serve as a specific target in the prevention of arterial thrombosis in vivo. The last part of this project is aimed at investigating the possible role of gap junctions in the propagation of endothelial flow-induced signaling.The proposed investigations should provide new insights into the mechanisms underlying myocardial infarction, stroke and peripheral artery disease, the major clinical consequences of atherosclerosis. Beyond such a clarification of the mechanism involved, this work may identify a novel potential target for treatment of arterial thrombosis.