Innate and adaptive immunity in cardiovascular calcification

  • Author Footnotes
    1 These authors contributed equally to this work.
    Livia S.A. Passos
    1 These authors contributed equally to this work.
    Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Adrien Lupieri
    1 These authors contributed equally to this work.
    Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
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  • Dakota Becker-Greene
    Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
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  • Elena Aikawa
    Corresponding author. Brigham and Women's Hospital, Harvard Medical School, 17th Floor CLS Building, 3 Blackfan Street, Boston, MA, 02115, USA.
    Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Department of Pathology, Sechenov First Moscow State Medical University, Moscow, 119992, Russia
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  • Author Footnotes
    1 These authors contributed equally to this work.


      • Cardiovascular calcification is increasing in prevalence and remains a contributor to morbidity and mortality.
      • Calcium deposition is associated with progression and severity of cardiovascular disease and linked to cardiovascular risk.
      • The lack of therapeutic or preventative strategies in cardiovascular calcification is an indicator of disease complexity.
      • Cardiovascular calcification is regulated through an integrated combination of innate and adaptive immune responses.
      • Immunomodulatory drugs possess the potential to target and treat calcification.


      Despite the focus placed on cardiovascular research, the prevalence of vascular and valvular calcification is increasing and remains a leading contributor of cardiovascular morbidity and mortality. Accumulating studies provide evidence that cardiovascular calcification is an inflammatory disease in which innate immune signaling becomes sustained and/or excessive, shaping a deleterious adaptive response. The triggering immune factors and subsequent inflammatory events surrounding cardiovascular calcification remain poorly understood, despite sustained significant research interest and support in the field. Most studies on cardiovascular calcification focus on innate cells, particularly macrophages’ ability to release pro-osteogenic cytokines and calcification-prone extracellular vesicles and apoptotic bodies. Even though substantial evidence demonstrates that macrophages are key components in triggering cardiovascular calcification, the crosstalk between innate and adaptive immune cell components has not been adequately addressed. The only therapeutic options currently used are invasive procedures by surgery or transcatheter intervention. However, no approved drug has shown prophylactic or therapeutic effectiveness. Conventional diagnostic imaging is currently the best method for detecting, measuring, and assisting in the treatment of calcification. However, these common imaging modalities are unable to detect early subclinical stages of disease at the level of microcalcifications; therefore, the vast majority of patients are diagnosed when macrocalcifications are already established. In this review, we unravel the current knowledge of how innate and adaptive immunity regulate cardiovascular calcification; and put forward differences and similarities between vascular and valvular disease. Additionally, we highlight potential immunomodulatory drugs with the potential to target calcification and propose avenues in need of further translational inquiry.

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