The role of monocyte reprogramming in chronic venous thrombosis

• Applicant: Fatemeh Zare-Shahneh, Ph.D.
• Subject Area: Cardiology, Angiology ; Cardiac and Vascular Surgery ; Immunology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 507777753

Deep vein thrombosis is associated with long-term complications, including recurrent venous embolism, post-thrombotic syndrome, and chronic thromboembolic pulmonary hypertension. Despite initial management of symptomatic acute events, patients remain at high risk for recurrence and predisposed to developing longer-term thrombo-inflammatory complications. The influences of the first event of DVT in the recurrence of VTE and thrombotic sequelae remain unknown. Recent advances suggest that the interactions of inflammatory processes with underlying cardiovascular disease may promote long-lasting functional changes of monocytes, specifically the appearance of so-called trained cells. The inflammatory response induced by the thrombus formation recruits a significant number of circulating myeloid cells to the site of thrombotic damage. The long-term chronic inflammation during clot growth may affect the bone marrow myelopoiesis and monocyte profile and therefore contributes to the progression of further VTE complications. Therefore, we aim to systematically analyze the development of trained monocytes in thrombotic disease pathology and recurrence. Working steps consist in investigating the regulatory impact, phenotypic profiling, and functional evaluation of innate immune alteration. This study will bring us closer to an understanding of the pathogenesis of VTE recurrence that can be successfully translated to humans and improve our knowledge in cardiovascular medicine.

• DFG Programme: Research Grants