Skip to main content
The William Harvey Research Institute - Faculty of Medicine and Dentistry

Breadcrumb

  1. WHRI
  2. Study
  3. Barts Charity Doctoral Training Programme
  4. Projects
  5. BC-DTP_2026_25

Enriched Marine Oil Supplement as a Novel Therapeutic Approach for the Management of Inflamatory Arthritis-Associated Cardiomyopathy

Code: BC-DTP_2026_25

Title: Enriched Marine Oil Supplement as a Novel Therapeutic Approach for the Management of Inflamatory Arthritis-Associated Cardiomyopathy

Primary Supervisor: Jianmin Chen

Email: jianmin.chen@qmul.ac.uk

Institute: William Harvey Research Institute

Secondary Supervisor: Jes Dalli

Email: j.dalli@qmul.ac.uk

Institute: William Harvey Research Institute

Lay Summary:

PROBLEM:

Rheumatoid arthritis (RA) is a long-term inflammatory disease that mainly affects the joints, but it can also silently damage the heart, contributing to nearly half of RA‑related deaths. A major complication is heart failure with preserved ejection fraction (HFpEF), where the heart becomes stiff and struggles to fill properly. Current anti‑RA medicines do not prevent and may even worsen this heart problem, so the underlying causes remain poorly understood.

APPROACH:

This project aims to uncover why heart failure develops in RA and to test a dietary supplement that could help prevent it. The work focuses on specialised pro‑resolving lipid mediators (SPMs)—natural molecules that switch off inflammation and promote healing—which appear impaired in arthritic hearts.

SOLUTION:

Two arthritis–heart disease mouse models will be used to test how a safe essential fatty acid supplement can protect the heart by boosting SPM levels. Meanwhile, SPMs will be measured in blood samples (obtained through a Barts Charity‑funded Clinical Fellowship) from East London RA patients to see whether the SPM changes identified in mice also occur in patients with heart problems. Key SPMs will also be tested in human immune–fibroblast co‑cultures to understand how they reduce heart inflammation.

IMPACT & NOVELTY:

East London is home to diverse, often underserved communities disproportionately affected by chronic inflammatory diseases, frequently compounded by co‑morbidities. Including local RA patients ensures the research reflects real‑world need. The expected benefits—better screening, earlier detection, and a safe, low‑cost supplement—could reduce RA‑related heart disease locally and guide prevention efforts in similar communities elsewhere.

Aims:

Aim #1: Efficacy of the EFA supplement on ‘arthritic cardiomyopathy’ in K/BxN mice (Months 1–18).

Aim #2: Target validation in a second model of diastolic dysfunction in arthritis using Alox15 knockout mice (Months 16–36).

Aim #3: Translational potential of the EFA supplement in RA patients with cardiomyopathy (Months 21–40).

References:

  1. Conrad, N.; Verbeke, G.; Molenberghs, G.; Goetschalckx, L.; Callender, T.; Cambridge, G.; Mason, J. C.; Rahimi, K.; McMurray, J. J. V.; Verbakel, J. Y., Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK. Lancet 2022, 400 (10354), 733–743.
  2. Chen, J.; Norling, L. V.; Cooper, D., Cardiac Dysfunction in Rheumatoid Arthritis: The Role of Inflammation. Cells 2021, 10 (4).
  3. Peh, H. Y.; Chen, J., Pro-resolving lipid mediators and therapeutic innovations in resolution of inflammation. Pharmacol Ther 2025, 265, 108753.
  4. Chen, J.; Norling, L. V.; Mesa, J. G.; Silva, M. P.; Burton, S. E.; Reutelingsperger, C.; Perretti, M.; Cooper, D., Annexin A1 attenuates cardiac diastolic dysfunction in mice with inflammatory arthritis. Proc Natl Acad Sci U S A 2021, 118 (38).
  5. Margraf, A.; Chen, J.; Christoforou, M.; Claria-Ribas, P.; Henriques Schneider, A.; Cecconello, C.; Bu, W.; Imbert, P. R. C.; Wright, T. D.; Russo, S.; Blacksell, I. A.; Koenis, D. S.; Dalli, J.; Lupisella, J. A.; Wurtz, N. R.; Garcia, R. A.; Cooper, D.; Norling, L. V.; Perretti, M., Formyl-peptide receptor type 2 activation mitigates heart and lung damage in inflammatory arthritis. EMBO Mol Med 2025.
  6. Arnardottir, H.; Thul, S.; Pawelzik, S. C.; Karadimou, G.; Artiach, G.; Gallina, A. L.; Mysdotter, V.; Carracedo, M.; Tarnawski, L.; Caravaca, A. S.; Baumgartner, R.; Ketelhuth, D. F.; Olofsson, P. S.; Paulsson-Berne, G.; Hansson, G. K.; Bäck, M., The resolvin D1 receptor GPR32 transduces inflammation resolution and atheroprotection. J Clin Invest 2021, 131 (24).
  7. Bardin, M.; Pawelzik, S. C.; Lagrange, J.; Mahdi, A.; Arnardottir, H.; Regnault, V.; Fève, B.; Lacolley, P.; Michel, J. B.; Mercier, N.; Bäck, M., The resolvin D2–GPR18 axis is expressed in human coronary atherosclerosis and transduces atheroprotection in apolipoprotein E deficient mice. Biochem Pharmacol 2022, 201, 115075.
  8. Salic, K.; Morrison, M. C.; Verschuren, L.; Wielinga, P. Y.; Wu, L.; Kleemann, R.; Gjorstrup, P.; Kooistra, T., Resolvin E1 attenuates atherosclerosis in absence of cholesterol-lowering effects and on top of atorvastatin. Atherosclerosis 2016, 250, 158–165.
  9. Viola, J. R.; Lemnitzer, P.; Jansen, Y.; Csaba, G.; Winter, C.; Neideck, C.; Silvestre-Roig, C.; Dittmar, G.; Döring, Y.; Drechsler, M.; Weber, C.; Zimmer, R.; Cenac, N.; Soehnlein, O., Resolving Lipid Mediators Maresin 1 and Resolvin D2 Prevent Atheroprogression in Mice. Circ Res 2016, 119 (9), 1030–1038.
  10. Liu, R.; Li, Z.; Wang, Q., Resolvin D1 Attenuates Myocardial Infarction in a Rodent Model with the Participation of the HMGB1 Pathway. Cardiovasc Drugs Ther 2019, 33 (4), 399–406.
  11. Liu, G.; Liu, Q.; Shen, Y.; Kong, D.; Gong, Y.; Tao, B.; Chen, G.; Guo, S.; Li, J.; Zuo, S.; Yu, Y.; Yin, H.; Zhang, L.; Zhou, B.; Funk, C. D.; Zhang, J., Early treatment with Resolvin E1 facilitates myocardial recovery from ischaemia in mice. Br J Pharmacol 2018, 175 (8), 1205–1216.
  12. Wang, F.; Gong, Y.; Chen, T.; Li, B.; Zhang, W.; Yin, L.; Zhao, H.; Tang, Y.; Wang, X.; Huang, C., Maresin1 ameliorates ventricular remodelling and arrhythmia in mice models of myocardial infarction via NRF2/HO-1 and TLR4/NF-kB signalling. Int Immunopharmacol 2022, 113 (Pt A), 109369.
  13. Chen, J.; Purvis, G. S. D.; Collotta, D.; Al Zoubi, S.; Sugimoto, M. A.; Cacace, A.; Martin, L.; Colas, R. A.; Collino, M.; Dalli, J.; Thiemermann, C., RvE1 Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction and Enhances Bacterial Clearance. Front Immunol 2020, 11, 2080.
  14. Federti, E.; Mattoscio, D.; Recchiuti, A.; Matte, A.; Monti, M.; Cozzolino, F.; Iezzi, M.; Ceci, M.; Ghigo, A.; Tolosano, E.; Siciliano, A.; Ceolan, J.; Riccardi, V.; Gremese, E.; Brugnara, C.; De Franceschi, L., 17(R)-Resolvin D1 protects against sickle cell-related inflammatory cardiomyopathy in humanized mice. Blood 2025, 145 (17), 1915–1928.
  15. Calder, P. C., Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol 2013, 75 (3), 645–662.
  16. Bhatt, D. L.; Steg, P. G.; Miller, M.; Brinton, E. A.; Jacobson, T. A.; Ketchum, S. B.; Doyle, R. T., Jr.; Juliano, R. A.; Jiao, L.; Granowitz, C.; Tardif, J. C.; Ballantyne, C. M.; Investigators, R.-I., Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019, 380 (1), 11–22.
  17. Jawad, M. A.; O'Keefe, J. H.; Tintle, N.; O'Keefe, E. L.; Franco, W. G.; Djousse, L.; Ryder, N.; Harris, W. S., Association of Plasma Omega-3 Levels With Incident Heart Failure and Related Mortalities. Mayo Clin Proc 2024, 99 (12), 1895–1904.
  18. Xie, L.; Zhen, P.; Wei, Q.; Yu, F.; Song, S.; Tong, J., Effects of omega-3 polyunsaturated fatty acids supplementation for patients with cardiovascular disease risks: a dose-response meta-analysis. Am J Transl Res 2021, 13 (8), 8526–8539.
  19. Olivares-Gonzalez, L.; Velasco, S.; Gallego, I.; Esteban-Medina, M.; Puras, G.; Loucera, C.; Martinez-Romero, A.; Pena-Chilet, M.; Pedraz, J. L.; Rodrigo, R., An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice. Antioxidants (Basel) 2022, 12 (1).
  20. Souza, P. R.; Marques, R. M.; Gomez, E. A.; Colas, R. A.; De Matteis, R.; Zak, A.; Patel, M.; Collier, D. J.; Dalli, J., Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses: A Randomized Double-Blind Placebo-Controlled Study. Circ Res 2020, 126 (1), 75–90.
  21. Irun, P.; Carrera-Lasfuentes, P.; Sanchez-Luengo, M.; Belio, U.; Domper-Arnal, M. J.; Higuera, G. A.; Hawkins, M.; de la Rosa, X.; Lanas, A., Pharmacokinetics and Changes in Lipid Mediator Profiling after Consumption of Specialized Pro-Resolving Lipid-Mediator-Enriched Marine Oil in Healthy Subjects. Int J Mol Sci 2023, 24 (22).
  22. Schaller, M. S.; Chen, M.; Colas, R. A.; Sorrentino, T. A.; Lazar, A. A.; Grenon, S. M.; Dalli, J.; Conte, M. S., Treatment With a Marine Oil Supplement Alters Lipid Mediators and Leukocyte Phenotype in Healthy Patients and Those With Peripheral Artery Disease. J Am Heart Assoc 2020, 9 (15), e016113.
  23. Moller, I.; Rodas, G.; Villalon, J. M.; Rodas, J. A.; Angulo, F.; Martinez, N.; Verges, J., Randomized, double-blind, placebo-controlled study to evaluate the effect of treatment with an SPMs-enriched oil on chronic pain and inflammation, functionality, and quality of life in patients with symptomatic knee osteoarthritis: GAUDI study. J Transl Med 2023, 21 (1), 423.
  24. Koenis, D. S.; de Matteis, R.; Rajeeve, V.; Cutillas, P.; Dalli, J., Efferocyte-Derived MCTRs Metabolically Prime Macrophages for Continual Efferocytosis via Rac1-Mediated Activation of Glycolysis. Adv Sci (Weinh) 2024, 11 (7), e2304690.
  25. Gomez, E. A.; Colas, R. A.; Souza, P. R.; Hands, R.; Lewis, M. J.; Bessant, C.; Pitzalis, C.; Dalli, J., Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis. Nat Commun 2020, 11 (1), 5420.
Back to top