Journal of Inflammation Research

Thromboinflammation in Atherosclerotic Cardiovascular Disease: From Plaque Destabilization to Precision Therapeutics

The Journal of Inflammation Research is pleased to welcome you to submit your research to the Article Collection "Thromboinflammation in Atherosclerotic Cardiovascular Disease: From Plaque Destabilization to Precision Therapeutics".

Thromboinflammation, the bidirectional and self-amplifying interplay between coagulation and innate immunity, has emerged as a central driver of atherosclerotic plaque destabilization and acute cardiovascular events. Beyond the traditional view of thrombosis as a late consequence of plaque rupture, current evidence indicates that inflammatory and hemostatic pathways are dynamically intertwined throughout the natural history of atherosclerosis, from lesion initiation to clinical complications. Endothelial dysfunction, platelet activation, leukocyte recruitment, inflammasome signaling, and fibrin formation participate in a tightly coordinated network that shapes plaque biology and thrombotic risk. This evolving framework challenges purely structural concepts of plaque vulnerability and highlights the importance of immunothrombotic activity within the arterial wall and circulation. As mechanistic and translational studies continue to refine this field, thromboinflammation is increasingly recognized not only as a pathogenic concept, but also as a promising lens through which to reinterpret risk stratification, disease heterogeneity, and therapeutic opportunity in cardiovascular inflammation.

This topic is important because thromboinflammation helps explain why major cardiovascular events still occur despite substantial advances in lipid lowering, antiplatelet therapy, and revascularization. Residual inflammatory and thrombotic risk remains a major clinical challenge, and a more integrated understanding of immune-coagulative cross-talk may improve both prevention and treatment. Recent work has questioned the binary distinction between stable and unstable plaques, suggesting instead that clinically silent lesions may retain persistent thromboinflammatory activity and contribute to the vulnerable patient phenotype. At the same time, plaque rupture and plaque erosion are increasingly understood as distinct biological entities, with different cellular drivers and potentially different therapeutic implications. Neutrophils, neutrophil extracellular traps, NLRP3 inflammasome signaling, complement activation, tissue factor release, and platelet mediated amplification have all become major areas of investigation. Clarifying these mechanisms is essential for identifying biomarkers, refining imaging strategies, and developing safer precision therapies that modulate inflammation without unacceptable bleeding risk.

This Article Collection welcomes contributions addressing the mechanistic, translational, and clinical dimensions of thromboinflammation in atherosclerotic cardiovascular disease, in line with the scope of the Journal of Inflammation Research. Topics of particular interest include:

• The immunobiology of plaque activation and destabilization
• The transition from the vulnerable plaque paradigm to the vulnerable patient model
• Differential mechanisms of plaque rupture and plaque erosion
• Neutrophil recruitment, NETosis, and endothelial injury
• Inflammasome pathways, especially NLRP3, and their interaction with monocytes, macrophages, and platelets
• Cross-talk among coagulation, complement, and contact system cascades
• Biomarkers of thromboinflammatory risk
• Multimodal imaging of vascular inflammation
• Age-related immune dysregulation and thromboinflammaging
• Emerging anti-inflammatory, antithrombotic, and combined therapeutic strategies

The Collection will consider all article types accepted by the journal, with particular interest in original research articles, narrative or systematic reviews, brief reports, and perspectives/opinion pieces that bridge experimental discovery with clinical relevance.

Keywords: Thromboinflammation; Atherosclerosis; Plaque destabilization; Neutrophil extracellular traps; NLRP3 inflammasome 

Meet the Guest Advisors

Dr. G. Miceli serves as Attending Physician in the Unit of Internal Medicine with Stroke Care at the University Hospital P. Giaccone, Palermo, Italy, where he is also Head of Neurosonology outpatient clinic and acts as Consultant Internist. His clinical, scientific, and
academic activity is centered on internal medicine, cerebrovascular disease, and the non-invasive evaluation of vascular function and cerebral hemodynamics. He has developed advanced expertise in vascular echo, color Doppler and neurosonology, applying these methodologies to the study of cerebral hemodynamics as a surrogate marker of cardio-cerebrovascular risk in selected clinical conditions such as acute ischemic stroke, liver cirrhosis, human immunodeficiency virus infection, and heart failure. His scientific activity has further integrated the study of thromboinflammation and carotid plaque instability with emerging applications of artificial intelligence, with the aim of refining strategies for cardiovascular and cerebrovascular prevention. A distinctive line of his research concerns the pathophysiology of the carotid plaque. On the basis of these studies, he contributed to the development of a conceptual framework intended to overcome the traditional binary distinction between stable and unstable plaque, proposing instead a tripartite classification consisting of stable silent plaque, stable active plaque, and unstable plaque. Within the same perspective, he also contributed to the formulation of the concept of chronic carotid syndrome, a chronic carotid atherosclerotic condition characterized by persistent plaque activity and ongoing cerebrovascular risk, even in the absence of stroke and other acute clinical manifestations. He has conducted several clinical studies in the fields
of hypertension, ischemic stroke, atherosclerosis, botulinum intoxication, and cirrhosis, contributing to the advancement of research in internal medicine and vascular prevention.

Dr. Mario Daidone is a tenure-track researcher in Internal Medicine (MED/09) at the University of Palermo, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties “G. D’Alessandro”. His clinical and scientific activity is carried out within the Internal Medicine and Stroke Care Unit of the University Hospital “Paolo Giaccone” of Palermo, a setting devoted to complex internal medicine patients with vascular, cerebrovascular and cardiometabolic comorbidities. Dr. Daidone’s research profile is centred on internal medicine, vascular medicine and cerebrovascular prevention, with a specific focus on the interaction between cardiovascular risk factors, systemic inflammation, endothelial dysfunction, atrial fibrillation, ischemic stroke and cognitive decline. Dr. Daidone has contributed to translational biomarker studies addressing ischemic injury, platelet activation, systemic inflammation, endothelial dysfunction and neuroglial damage. His work includes the analysis of osteopontin, platelet factor 4, IP-10, soluble thrombomodulin, UCH-L1, GFAP and FABP3, with the aim of identifying biological signatures linking vascular inflammation, platelet activation and neuronal/glial injury. Dr. Daidone has experience in building multicentre clinical datasets and applying supervised machine-learning approaches to predict cognitive decline and cerebrovascular outcomes. His methodological skills include dataset harmonisation, management of missing data, variable coding, stratified train/test splitting, repeated cross-validation, class imbalance handling, ROC-AUC and precision-recall analysis, confusion matrix interpretation and permutation-based feature importance.