Targeting platelet-neutrophil interactions in giant-cell arteritis
Mattia Baldini, Angelo A Manfredi, Norma Maugeri1
1NM, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy. maugeri.norma@hsr.it.
Insights
Giant-cell arteritis (GCA) involves inflammation of large arteries, increasing disability from ischemic events. Understanding blood cell interactions may reveal new treatments beyond aspirin and steroids for preventing vessel occlusion.
Area of Science:
- Rheumatology
- Vascular Medicine
- Immunology
Background:
- Giant-cell arteritis (GCA) is a prevalent vasculitis in the elderly, often leading to significant disability due to ischemic events.
- Current treatments like corticosteroids are slow-acting and not universally effective, highlighting the need for improved therapeutic strategies.
- The precise mechanisms leading to vessel occlusion in GCA remain unclear, despite advances in understanding arterial inflammation.
Purpose of the Study:
- To investigate the role of interactions between circulating blood cells in the pathogenesis of ischemic events in GCA.
- To identify molecular targets for novel therapeutics aimed at preventing GCA-associated ischemia.
- To explore the potential of targeting blood cell cross-talk for more effective and specific GCA treatment.
Main Methods:
- Analysis of cohort studies examining risk factors and aspirin efficacy in GCA patients.
- Investigation of platelet and leukocyte activation and their interactions in GCA patients.
- Assessment of tissue factor expression by circulating leukocytes in GCA patients.
Main Results:
- Inconsistent results from cohort studies on aspirin's efficiency in GCA.
- Evidence of activated circulating platelets and their interaction with leukocytes in GCA patients.
- Frequent expression of tissue factor by circulating leukocytes in GCA patients.
Conclusions:
- The cross-talk between blood cells and the inflamed vessel wall is a critical factor in GCA.
- Targeting molecular interactions between platelets and leukocytes presents a promising therapeutic avenue.
- Novel treatments focusing on these cellular interactions could offer superior efficacy and specificity compared to current therapies.
Abstract:
Giant-cell arteritis (GCA) is the most common vasculitis affecting large vessels in the elderly. It is associated with ischemic events that account for important disability. Despite the increasing insight in the mechanisms involved in the arterial wall inflammation, the events that lead to eventual occlusion of the vessels lumen are unknown. Cohort studies on risk factors for ischemic events and aspirin efficiency in GCA provide inconsistent results. Corticosteroids, which prevent the worsening or the recurrence of ischemia in the majority of patients, are slow-acting and not effective in all patients. The interaction between circulating activated platelets and leukocytes contributes in acute myocardial infarction and other ischemic diseases to determine the prothrombotic and inflammatory characteristics of blood cells. The activation of circulating platelets, their interaction with leukocytes and the expression of tissue factor by circulating leukocytes frequently occur in patients with GCA. The molecular characterization of the cross-talk between blood cells and the inflamed vessel wall could yield molecular targets for novel therapeutics, more effective than aspirin in preventing ischemic events and more specific than steroids in their treatment.
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