Uli Schotten: Coagulation Factors May Influence Cardiac Remodelling
Uli Schotten, Professor and Chair of Physiology at Maastricht University, The Netherlands, Board of Directors of the Network of Competence in Atrial Fibrillation (AFNET), Germany, shared a post on LinkedIn:
“What do coagulation factors have to do with the size of atrial cardiomyocytes? Quite a lot, apparently!
We usually think of coagulation factors in the context of blood clotting and stroke prevention. But they appear to have important functions far beyond haemostasis.
In a new study published in Thrombosis and Haemostasis, Elisa D’Alessandro and our collaborators demonstrate that treatment with the factor Xa inhibitor rivaroxaban completely prevents atrial cardiomyocyte hypertrophy in a goat model of persistent AF.
Interestingly, experiments with human iPSC-derived atrial-like cardiomyocytes indicate that thrombin can directly activate pro-hypertrophic signalling through protease-activated receptor-1 (PAR-1).
This builds on our earlier work with Henri Spronk and our colleagues from the RACE-V consortium, published in the European Heart Journal in 2017, in which we demonstrated that hypercoagulability promotes atrial fibrosis and contributes to the development of a substrate for atrial fibrillation.
Together, these studies suggest that activated coagulation factors are much more than mediators of thrombosis. They can influence fibroblast activation, inflammation and even cardiomyocyte hypertrophy.
Could some of these non-haemostatic effects become therapeutic targets?
This is an intriguing possibility, particularly in the context of potential organ-protective effects of anticoagulation beyond stroke prevention.
Of course, these are experimental findings, and whether such effects translate into clinically meaningful protection in patients remains to be established.
Congratulations to Elisa involved in this beautiful collaborative work!
Again, a great contribution from our EmbRACE consortium funded by the Dutch Heart Foundation and our MAESTRIA network!”
Title: Rivaroxaban Treatment Prevents Atrial Myocyte Hypertrophy in Goats with Persistent Atrial Fibrillation by Inhibition of Protease-Activated Receptor-1
Authors: Elisa D’Alessandro, Billy Scaf, Dragan Opačić, Arne van Hunnik, Vladimír Sobota, Marion Kuiper, Marian Viola, Thomas Hutschalik, Marianna Langione, Josè M. Pioner, Chantal Munts, Jorik Simons, Joris Winters, Aaron Isaacs, Stefan Heitmeier, Monika Stoll, René van Oerle, Hugo ten Cate, Henri M. H. Spronk, Sander Verheule, Frans A. van Nieuwenhoven, Ulrich Schotten
Read the Full Article on Thrombosis and Haemostasis
Title: Hypercoagulability causes atrial fibrosis and promotes atrial fibrillation
Authors: Henri M.H. Spronk, Anne Margreet De Jong, Sander Verheule, Hetty C. De Boer, Alexander H. Maass, Dennis H. Lau, Michiel Rienstra, Arne van Hunnik, Marion Kuiper, Stijn Lumeij, Stef Zeemering, Dominik Linz, Pieter Willem Kamphuisen, Hugo ten Cate, Harry J. Crijns, Isabelle C. Van Gelder, Anton Jan van Zonneveld, Ulrich Schotten
Read the Full Article on European Heart Journal
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