Unit of Molecular Biology of Thrombosis in Cardiovascular Diseases

Head of the Unit

Marina Camera, PhD

The primary objective of the research conducted by the Unit is to improve thrombotic risk stratification in patients with cardiovascular disease, with the ultimate goal of providing a scientific rationale to support the optimization and personalization of pharmacological treatment. This objective is pursued through the identification of circulating biomarkers capable of predicting thrombotic risk.

To achieve these goals, the Unit leverages its extensive expertise in laboratory-to-bedside research programs, together with a strong background in cardiovascular pharmacology—particularly in drugs that modulate platelet function—and in the mechanisms regulating hemostasis and thrombosis. This expertise is essential for understanding the molecular mechanisms involved in:

  1. The pathophysiology of thrombotic complications associated with cardiovascular diseases;
  2. The interindividual variability in response to antiplatelet therapy.

Within this framework, the Unit’s research programs have evolved over the years around three key players:

  • Platelets, the principal cellular components of thrombi;
  • Tissue Factor (TF), the key protein responsible for triggering the blood coagulation cascade;
  • Circulating microvesicles (MVs), whose molecular signature provides valuable insights into dysfunctional cellular compartments across a variety of clinical settings.

By investigating these three interconnected elements, the Unit aims to advance the understanding of thrombosis mechanisms, identify novel prognostic and therapeutic biomarkers, and contribute to the development of more effective and individualized strategies for the prevention and treatment of cardiovascular complications.

Selected Projects

  • Novel Pathogenic Mechanisms in Acute Coronary Syndrome: Platelet Tissue Factor

    One of the Unit’s most significant contributions has been the discovery and characterization of Tissue Factor (TF) expression in circulating human platelets. TF expression is significantly increased in patients at high cardiovascular risk, contributing to the development of a prothrombotic phenotype.

    A study conducted by this Research Unit involving approximately 1,000 patients with coronary artery disease (CAD) enrolled at the Monzino Cardiology Center (CCM) demonstrated the predictive value of this biomarker for cardiovascular mortality. This finding is particularly relevant in the context of the well-recognized interindividual variability in response to antiplatelet therapy, as platelet TF expression is modulated by antiplatelet agents, including P2Y12 receptor inhibitors.

    Pathophysiological Mechanisms Involved in Migraine Manifestations in Patients with Patent Foramen Ovale (PFO)

    Another major research program developed over recent years focuses on identifying the pathophysiological mechanisms underlying the clinical manifestations of cardiovascular diseases.

    The Unit has recently demonstrated that patients with patent foramen ovale (PFO) and migraine with aura (MA) exhibit a prothrombotic platelet phenotype. This phenotype is driven by oxidative stress, which increases the number of circulating platelets expressing Tissue Factor, thereby enhancing their procoagulant properties.

    Notably, this prothrombotic phenotype has been shown to reverse following correction of the cardiac defect, in parallel with the remission of migraine symptoms. These findings provide new insights into the biological mechanisms linking PFO and migraine, while suggesting potential therapeutic targets for affected patients.

    Circulating Microvesicles in Coronary Artery Disease

    Another key research area of the Unit focuses on characterizing the contribution of circulating extracellular vesicles (EVs), important mediators of intercellular communication that play a pivotal role in several pathological processes, including coronary artery disease and atherothrombosis.

    Thanks to the state-of-the-art instrumentation available within the CCM research laboratories, ongoing studies are aimed at defining the procoagulant contribution of the different vesicle populations released by circulating blood cells. The ultimate objective is to identify novel and promising therapeutic targets that may support future strategies to reduce the blood’s procoagulant potential and prevent thrombotic cardiovascular events.

best publications in the last three years

    • Alterations in platelets during SARS-CoV-2 infection. Brambilla M., Canzano,P., Becchetti A., Tremoli E., Camera, M. Platelets, 2022, 33(2), pp. 192–199
    • Migraine in Patients Undergoing PFO Closure: Characterization of a Platelet-associated Pathophysiological Mechanism. The LEARNER Study. Trabattoni D, Brambilla M, Canzano P, Becchetti A, Teruzzi G, Benedetta Porro, Susanna Fiorelli, Emanuela Muratori, Calogero Tedesco, Fabrizio Veglia, Piero Montorsi, Antonio L. Bartorelli, Elena Tremoli Marina Camera. JACC Basic Transl Sci. 2022 Apr 13;7(6):525-540
    • Cell surface platelet Tissue Factor expression: regulation by P2Y12 and link to residual platelet reactivity. M. Brambilla, A. Becchetti, G.E. Rovati, N. Cosentino, M. Conti, P. Canzano, P.L.A. Giesen, A. Loffreda, A. Bonomi, M. Cattaneo, E. De Candia, GM. Podda, D. Trabattoni, P. Werba, J. Campodonico, C. Pinna, G. Marenzi, E. Tremoli, M. Camera. Arterioscler Thromb Vasc Biol. 2023 Oct;43(10):2042-2057.
    • Head-to-Head Comparison of Tissue Factor-Dependent Procoagulant Potential of Small and Large Extracellular Vesicles in Healthy Subjects and in Patients with SARS-CoV-2 Infection. Brambilla M, Frigerio R, Becchetti A, Gori A, Cretich M, Conti M, Mazza A, Pengo M, Camera M. Biology (Basel). 2023 Sep 13;12(9):1233.
    • Flow cytometry analysis of Tissue Factor expression in human platelets. Brambilla Marta, Becchetti Alessia, Nallio Kevin, Camera Marina. J Vis Exp 2024 Nov 22:(213).
    • Low-Grade Inflammation in Long COVID Syndrome Sustains a Persistent Platelet Activation Associated With Lung Impairment. Brambilla M, Fumoso F, Conti M, Becchetti A, Bozzi S, Mencarini T, Agostoni P, Mancini ME, Cosentino N, Bonomi A, Nallio K, Galotta A, Pengo M, Tortorici E, Bosco M, Cernigliaro F, Pinna C, Andreini D, Camera M. JACC Basic Transl Sci. 2024 Nov 27;10(1):20-39
    • Combining Colchicine and Antiplatelet Therapy to Tackle Atherothrombosis: A Paradigm in Transition? S. Giordano, M. Camera, M. Brambilla, G. Sarto, L. Spadafora, M. Bernardi, A. Iaconelli, D D’Amario, G. Biondi-Zoccai, AI Celia, E. Tremoli, G. Frati, DJ. Angiolillo, S Sciarretta, M. Galli. Int. J. Mol. Sci. 2025, 26, 1136.
    • Mechanisms sensitive to different drugs mediate a pro-adhesive and pro-thrombotic platelet phenotype in anti-phospholipid syndrome. Camera M, Brambilla M, Lonati PA, Becchetti A, Grossi C, Nallio K, Da Via A, Trespidi L, Borghi MO, Tedesco F, Meroni PL. Haematologica. 2025 Jul 3.
    • Biomarkers of in vivo platelet activation in coronary artery disease: a systematic review and meta-analysis: Communication from the SSC of the ISTH. Brambilla M, Josefsson EC, Ramstrom S, Di Minno A, Dario Di Minno MN, Gangatirkar P, Moujalled D, Becchetti A, Lordkipanidzé M, Camera M. J Thromb Haemost. 2025 Jul 18:S1538-7836(25)00438-6.

Staff

  • Marta Brambilla, PhD

    Maria Conti, PhD

    Alessia Becchetti, PhD

    Kevin Nallio, MSc