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Cited by 1,033Blood Coagulation and Thrombosis MechanismsPlatelet Disorders and TreatmentsComplement system in diseases

Interplay between inflammation and thrombosis in cardiovascular pathology

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Stark, Konstantin, Massberg, Steffen·2021·Nature Reviews Cardiology
DOI 10.1038/s41569-021-00552-1PMC PMC8100938
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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.

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  • When lipid metabolism is imbalanced, elevated levels of RC can lead to its infiltration into the arterial wall, causing cholesterol deposition beneath the endothelium and accelerating the formation of foam cells and lipid plaques, while provoking a low-grade inflammatory response, significantly increasing the risk of AS.

    “In summary, when lipid metabolism is imbalanced, elevated levels of RC can lead to its infiltration into the arterial wall, causing cholesterol deposition beneath the endothelium and accelerating the formation of foam cells and lipid plaques, while provoking a low-grade inflammatory response. These processes significantly increase the risk of AS.”

    From Remnant cholesterol, lipid ratios, and the severity of coronary artery lesions: a retrospective cohort study in patients with coronary heart disease (2025) · cites this paper as [32]

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Cited by

Sorted by citations

Authors
Stark, K., & Massberg, S.
Affiliations
LMU Klinikum (DE)
Corresponding author
  • Stark, Konstantin
  • Massberg, Steffen
ORCID
Venue
Nature Reviews Cardiology
Publisher
Springer Science and Business Media LLC
Published
2021-05-06
Volume
18
Issue
9
Pages
666-682
ISSN
  • 1759-5002 (ISSN-L)
  • 1759-5010
DOI
10.1038/s41569-021-00552-1
PMC
PMC8100938
OpenAlex
W3159729619
Cited by
1,033
References
14
Citations by year
2026: 240 · 2025: 254 · 2024: 221 · 2023: 187 · 2022: 104 · 2021: 26
FWCI
23.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Cardiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Deutsches Zentrum für Herz-Kreislaufforschung (MHA 1.4VD)
  • European Commission (HORIZON2020, 260309)
  • Deutsche Forschungsgemeinschaft (FOR2033, SFB 914, SFB1123, and Z01)
  • H2020 European Research Council (947611)
Topics
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
Keywords
immunothrombosis, thromboinflammation, inflammation, thrombosis, platelet activation, coagulation cascade, innate immunity, anti-inflammatory therapy, bleeding risk, myocardial infarction, stroke, venous thromboembolism, COVID-19 pandemic, cardiovascular disease
MeSH terms
COVID-19, Anti-Inflammatory Agents, Blood Coagulation, Fibrinolytic Agents, Humans, Immune System, Inflammation, Risk Factors, Thrombosis, Signal Transduction, Risk Assessment, Inflammation Mediators

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