title: Vascular pentraxin 3 controls arterial thrombosis by targeting collagen and fibrinogen induced platelets aggregation.
abstract: The long pentraxin PTX3 plays a non-redundant role during acute myocardial infarction, atherosclerosis and in the orchestration of tissue repair and remodeling during vascular injury, clotting and fibrin deposition. The aim of this work is to investigate the molecular mechanisms underlying the protective role of PTX3 during arterial thrombosis.
  
  
  
  PTX3 KO mice transplanted with bone marrow from WT or PTX3 KO mice presented a significant reduction in carotid artery blood flow following FeCl3 induced arterial thrombosis (-80.36±11.5% and -95.53±4.46%), while in WT mice transplanted with bone marrow from either WT or PTX3 KO mice, the reduction was less dramatic (-45.55±1.37% and -53.39±9.8%), thus pointing to a protective effect independent of a hematopoietic cell's derived PTX3. By using P-selectin/PTX3 double KO mice, we further excluded a role for P-selectin, a target of PTX3 released by neutrophils, in vascular protection played by PTX3. In agreement with a minor role for hematopoietic cell-derived PTX3, platelet activation (assessed by flow cytometric expression of markers of platelet activation) was similar in PTX3 KO and WT mice as were haemostatic properties. Histological analysis indicated that PTX3 localizes within the thrombus and the vessel wall, and specific experiments with the N-terminal and the C-terminal PTX3 domain showed the ability of PTX3 to selectively dampen either fibrinogen or collagen induced platelet adhesion and aggregation.
  
  
  
  PTX3 interacts with fibrinogen and collagen and, by dampening their pro-thrombotic effects, plays a protective role during arterial thrombosis.
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bonacina
authors.affiliation: IRCCS, Centro Cardiologico Monzino, Milan, Italy.
authors.forename: S S
authors.initials: SS
authors.lastname: Barbieri
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cutuli
authors.affiliation: IRCCS, Centro Cardiologico Monzino, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Amadio
authors.affiliation: IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Doni
authors.affiliation: IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sironi
authors.affiliation: IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Tartari
authors.affiliation: IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.affiliation: IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Bottazzi
authors.affiliation: IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Garlanda
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; IRCCS, Centro Cardiologico Monzino, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Tremoli
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; IRCCS Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it.
authors.forename: A L
authors.initials: AL
authors.lastname: Catapano
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; SISA Centre for the Study of Atherosclerosis, Bassini Hospital, Cinisello B, Milan, Italy; William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, UK. Electronic address: danilo.norata@unimi.it.
authors.forename: G D
authors.initials: GD
authors.lastname: Norata
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006487:Hemostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation; D060066:Protein Interaction Maps; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D003094:Collagen; D005340:Fibrinogen; D019007:P-Selectin; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: Arterial thrombosis; Collagen and fibrinogen; P-selectin; PTX3; Vessel wall