Confocal Blood Flow Videomicroscopy of Thrombus Formation over Human Arteries and Local Targeting of P2X7

Autor: Maria Lombardi, Ottavio Alfieri, Roberto Chiesa, Chiara Foglieni, Domenico Baccellieri, Maria Elena Mantione, David Ferrara, Patrizia Marchese
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
carotid plaque (CPL)
Pathology
Platelet Aggregation
030204 cardiovascular system & hematology
lcsh:Chemistry
0302 clinical medicine
Platelet
fibrin
lcsh:QH301-705.5
Spectroscopy
Microscopy
Confocal
Microscopy
Video
biology
Chemistry
internal mammary artery (IMA)
General Medicine
factor XI
Computer Science Applications
P2X purinoceptor 7 (P2X7)
Carotid Arteries
Coagulation
Blood Circulation
platelets
Blood Platelets
medicine.medical_specialty
Confocal
Thrombogenicity
Catalysis
Fibrin
Article
tissue factor (TF)
Inorganic Chemistry
03 medical and health sciences
Tissue factor
medicine
Humans
Physical and Theoretical Chemistry
Thrombus
Molecular Biology
Blood Coagulation
thrombogenicity
Organic Chemistry
Thrombosis
Blood flow
medicine.disease
Atherosclerosis
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Receptors
Purinergic P2X7
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 8
International Journal of Molecular Sciences, Vol 22, Iss 4066, p 4066 (2021)
ISSN: 1422-0067
Popis: Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy.
Databáze: OpenAIRE
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