Journal Article

The Role of Sterile Inflammation in Thrombosis: Consequences for Cardiovascular Disease and COVID‐19

Huwaikem, Mashael, Chowdhury, Kaustav, Khan, Gausal Azam, Albugami, Humood Fahm, Ghosh, Arjun

2025

Overview

Sterile inflammation (SI) is an inflammatory response triggered by the release of damage‐associated molecular patterns (DAMPs) from dying cells, distinct from normal inflammation in its origin from tissue injury and necrosis rather than microbial invasion. Circulating nucleic acids (CNAs), high‐mobility group box 1 (HMGB1), von Willebrand factor (vWF), and S100b protein are notable markers of SI, indicative of tissue damage and implicated in thrombotic disorders. Innate immunity, involving cells like macrophages and dendritic cells, recognizes DAMPs via pattern recognition receptors (PRRs) like Toll‐like receptors and NOD‐like receptors, initiating inflammatory signaling cascades central to SI and its cardiovascular consequences. Thrombosis, a common outcome of SI, underscores the intricate interplay between inflammation and hemostasis, with hypoxia exacerbating thrombotic risk through platelet activation and endothelial dysfunction. The established link between inflammation and thrombosis highlights the clinical significance of SI, where molecules like HMGB1, extracellular RNA (eRNA), and eDNA actively participate in thromboembolic disorders. SI’s relevance is particularly evident in COVID‐19‐induced thrombotic disorders, where dysregulated immune responses and endothelial dysfunction contribute to systemic inflammation and heightened thrombotic risk. Understanding SI’s mechanisms in these contexts is vital for developing targeted therapies to mitigate vascular complications and enhance patient outcomes in cardiovascular diseases and COVID‐19‐associated thrombosis.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Alarmins - metabolism / Antigen presenting cells / Antigens / Atherosclerosis / Autoimmune diseases / Blood clot / Blood clots / Blood coagulation factors / Cancer / Cardiac patients / Cardiovascular diseases / Cardiovascular Diseases - immunology / Cardiovascular Diseases - metabolism / Chemokines / Chromosomal proteins / Chronic illnesses / COVID-19 / COVID-19 - complications / COVID-19 - immunology / Cytokines / Darunavir / Dendritic cells / Diabetes / Heart attacks / Hemostasis / Heparan sulfate / HMGB1 protein / HMGB1 Protein - metabolism / Humans / Hypoxia / Immune response / Immune system / Immunity, Innate / Infections / Inflammation / Inflammation - complications / Inflammation - immunology / Inflammation - metabolism / Inflammatory diseases / Innate immunity / Ischemia / Long COVID / Lung diseases / Macrophages / Neutrophils / Pathogens / Pattern recognition receptors / Rheumatism / RNA / S100b protein / SARS-CoV-2 / Thromboembolism / Thrombosis / Thrombosis - etiology / Thrombosis - immunology / Thrombosis - metabolism / Trauma / Type 2 diabetes / Von Willebrand factor