Endotheliopathy and hemostasis disorders

Our team at the Paris Cardiovascular Research Center (PARCC) focuses on innovation in hemostasis, vascular biology, and regenerative medicine. With strong expertise and international recognition, our team is committed to excellence in science and dedicated to advancing major discoveries in vascular and thrombotic diseases. By integrating innovation, scientific rigor, and international collaboration, our mission is to develop cutting-edge therapeutic strategies for the benefit of both patients and the global scientific community.

We maintain active participation in major international structures, including several subcommittees of the International Society on Thrombosis and Hemostasis (ISTH): vascular biology and biomaterials (David Smadja), anticoagulants (Nicolas Gendron), and perioperative hemostasis (Anne Godier). We are also involved in numerous national and European research consortia, such as:

• INNOVTE (Investigation Network On Venous Thrombo-Embolism), a F-CRIN certified national research network,
• The French Society of Thrombosis and Hemostasis (SFTH),
• The TITANs Group (Thrombosis, Anticoagulants, and Antiplatelets),
• The MORPHEUS project (European Horizon Project for personalized anticoagulation in unprovoked venous thromboembolism),
• The GIHP (Perioperative Hemostasis Interest Group),
• And several Hospital-University Federations (FHU).

Our leadership and expertise have been recently recognized through the selection of our team in the PEPR Biotherapy initiative, a national investment program (France 2030), promoting innovative strategies in cell and tissue therapy. Our contribution to international consensus recommendations is also noteworthy. Under the coordination of David Smadja, our team authored two major international recommendations on standardizing endothelial progenitor cell cultures, facilitating harmonization of translational and regenerative research protocols.

In parallel, Nicolas Gendron and Anne Godier have played key roles in shaping national and international guidelines in hemostasis, including in antithrombotic therapies and perioperative management, consolidating our team’s role in both experimental and clinical expertise.

Thanks to our translational organization, we were able to respond rapidly to the emergence of the COVID-19 pandemic. From the first clinical signs of vascular and thrombotic complications caused by SARS-CoV-2, we launched the SARCODO study in February 2020, marking an early and decisive engagement in elucidating the mechanisms behind this new disease. This project, strengthened by extensive national and international collaborations, positioned our team as a key scientific actor in COVID-19–related vascular damage research.

Our findings have significantly contributed to a better understanding of thrombotic and endothelial complications during acute infection, the optimization of anticoagulant therapies, and the investigation of long-term vascular consequences, including in Long COVID. Today, building on this expertise, we are leading the first interventional clinical trial in Long COVID with respiratory symptoms: the BASECOVID trial, a project funded and supported nationally.

MISSION AND SCIENTIFIC OBJECTIVES

Our scientific goals center on the identification of novel mechanisms that lead to new therapeutic strategies in thrombosis, vascular and valvular pathologies, and regenerative medicine. Understanding how these mechanisms regulate core cellular functions and their involvement in disease is a major challenge.

To do so, we apply an integrated approach combining biochemical, genetic, cellular, and in vivo models, enabling a robust translational continuum from fundamental science to clinical applications. Our structure supports the development of novel therapeutic avenues and fosters innovation in cardiovascular science.

RESEARCH PROGRAMS

1. Vascular Regeneration with Endothelial Progenitor and Stem Cells

Co-led by Dr. Alexandre Lellouch

Our team has deeply investigated endothelial progenitor cells (EPCs), elucidating their roles in neovascularization, their interaction with coagulation pathways, and their function in ischemic repair and regeneration. We identified specific interactions with thrombin and thrombospondin, and proposed that small-sized stem cells may represent a primitive endothelial lineage in humans.

Our group led the drafting of the first international consensus on isolation and culture protocols for human endothelial progenitor cells, followed by a second article based on a global survey of current laboratory practices, confirming our leadership in standardization efforts for regenerative cell biology.

Under the coordination of Dr. Nicolas Fortunel, Research Director at the French Atomic Energy Commission (CEA), our team was awarded the PEPR Biotherapies France 2030 grant in 2023 for the project Bioengineered Skin France. This ambitious program seeks to enhance the regenerative potential of skin grafts using stem cell enrichment and prevascularization strategies involving EPCs, while reducing immune rejection.

We are currently developing allogeneic clinical applications of cord blood–derived EPCs in collaboration with the Saint-Louis Hospital Cell Therapy Center and a translational research team from Cedars-Sinai Hospital (Los Angeles).

2. valvular disease and Hemocompatibility of Biomaterials

Our team has significantly contributed to the evaluation of hemocompatibility in the Carmat Aeson® total artificial heart, a pulsatile biventricular assist device designed to closely replicate human cardiac physiology. The device includes a hybrid membrane and bovine pericardial valves, integrating it effectively into the human circulatory system.

Our studies demonstrated that the Aeson heart does not induce acquired von Willebrand syndrome, hemolysis, or thrombotic complications. Remarkably, endothelialization of the inner ventricular membrane was observed, which may explain the reduced anticoagulation needs in patients.

These results informed broader xenotransplantation research, notably in developing genetically modified porcine pericardial tissues expressing human anticoagulant proteins. This patented approach aims to increase the durability and reduce the calcification of bioprosthetic valves, with potential applications for younger patients and expanding eligibility for valve replacement therapies.

We are also conducting studies on the hemocompatibility of respiratory support devices, including novel CO₂ removal systems developed under the leadership of Prof. Jean-Luc Diehl. These projects seek to optimize gas exchange and improve biological tolerance in patients with severe respiratory failure.

3. COVID-19, Endotheliopathy, and Coagulopathy

As early as the late 2000s, our team proposed that the lung endothelium is a key organ in pulmonary disease, including pulmonary hypertension and idiopathic pulmonary fibrosis (IPF). We introduced circulating endothelial cells (CECs) as biomarkers for disease reversibility and treatment response.

With the emergence of COVID-19, we were among the first to investigate the vascular damage and coagulopathy caused by SARS-CoV-2. We launched the SARCODO study with early support from the French Ministry of Research, studying how the virus triggers endothelial dysfunction and microvascular thrombosis. Our findings showed that endothelial injury plays a critical role in the severe clotting abnormalities of COVID-19. We contributed evidence that early anticoagulation could reduce disease severity — an idea later confirmed by large randomized trials.

In March 2021, when the first thrombotic complications after COVID-19 vaccination were reported, the World Health Organization (WHO) commissioned us to assess the risks. His work concluded that thrombotic events were exceedingly rare, especially for mRNA vaccines, although rare cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) were documented following adenoviral vector vaccines.

Our team reported one of the first fatal cases of VITT in France and contributed to the scientific understanding of these new disorders. Dr. Nicolas Gendron characterized novel PF4-related thrombotic diseases, helping improve diagnostics and treatment strategies. Because antithrombotic treatments carry bleeding risks, our team also explores safer modalities to reduce hemorrhage in the context of trauma, anticoagulation, and platelet inhibition.

In 2023, our team demonstrated a link between pulmonary forms of Long COVID and elevated levels of vascular endothelial growth factor A (VEGF-A), a key regulator of abnormal vessel growth. Our work revealed that Long COVID is not a single disease, but a heterogeneous collection of syndromes with diverse clinical and biological profiles.These findings opened new therapeutic avenues, especially for patients with persistent respiratory symptoms. As a result, we launched BASECOVID, the first interventional trial for Long COVID, supported by the French ANRS-MIE agency for emerging diseases.

4. Coagulopathies and Endothelial Dysfunction

Co-led by Dr. Nicolas Gendron

We actively contribute to research on venous thrombosis, combining clinical studies, translational models, and genetic investigations. Through participation in INNOVTE and several genome-wide association studies (GWAS), we have identified new genetic determinants of thromboembolism.

Together with Prof. Isabelle Mahé, we also explore the relationship between cancer and thrombosis, as well as specific treatment strategies for cancer-associated thrombosis. Our team coordinated a multinational randomized trialdemonstrating the safety and efficacy of extended low-dose anticoagulation in cancer patients — a result that will directly inform clinical guidelines.

5. Endothelial Phenotyping in Vascular Ehlers-Danlos Syndrome (vEDS)

Co-led by Prof. Xavier Jeunemaître and Dr. Aurélien Philippe

Led by Prof. Xavier Jeunemaître, our team focuses on vascular Ehlers-Danlos Syndrome (vEDS), a rare and life-threatening connective tissue disorder. As a recognized national reference center for rare vascular diseases, we participate in clinical trials and international collaborations to improve understanding, diagnosis, and management of vEDS.