Interplay between inflammation and thrombosis in cardiovascular pathology

Nat Rev Cardiol. 2021 Sep;18(9):666-682. doi: 10.1038/s41569-021-00552-1. Epub 2021 May 6.

Abstract

Thrombosis is the most feared complication of cardiovascular diseases and a main cause of death worldwide, making it a major health-care challenge. Platelets and the coagulation cascade are effectively targeted by antithrombotic approaches, which carry an inherent risk of bleeding. Moreover, antithrombotics cannot completely prevent thrombotic events, implicating a therapeutic gap due to a third, not yet adequately addressed mechanism, namely inflammation. In this Review, we discuss how the synergy between inflammation and thrombosis drives thrombotic diseases. We focus on the huge potential of anti-inflammatory strategies to target cardiovascular pathologies. Findings in the past decade have uncovered a sophisticated connection between innate immunity, platelet activation and coagulation, termed immunothrombosis. Immunothrombosis is an important host defence mechanism to limit systemic spreading of pathogens through the bloodstream. However, the aberrant activation of immunothrombosis in cardiovascular diseases causes myocardial infarction, stroke and venous thromboembolism. The clinical relevance of aberrant immunothrombosis, referred to as thromboinflammation, is supported by the increased risk of cardiovascular events in patients with inflammatory diseases but also during infections, including in COVID-19. Clinical trials in the past 4 years have confirmed the anti-ischaemic effects of anti-inflammatory strategies, backing the concept of a prothrombotic function of inflammation. Targeting inflammation to prevent thrombosis leaves haemostasis mainly unaffected, circumventing the risk of bleeding associated with current approaches. Considering the growing number of anti-inflammatory therapies, it is crucial to appreciate their potential in covering therapeutic gaps in cardiovascular diseases.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Blood Coagulation / drug effects*
  • COVID-19 / blood
  • COVID-19 / immunology
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Immune System / drug effects*
  • Immune System / immunology
  • Immune System / metabolism
  • Inflammation / blood
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Risk Assessment
  • Risk Factors
  • Signal Transduction
  • Thrombosis / blood
  • Thrombosis / immunology
  • Thrombosis / prevention & control*

Substances

  • Anti-Inflammatory Agents
  • Fibrinolytic Agents
  • Inflammation Mediators