title: Losartan and captopril treatment rescue normal thrombus formation in microfibril associated glycoprotein-1 (MAGP1) deficient mice.
abstract: BACKGROUND
  MAGP1 is a glycoprotein present in the elastic fibers and is a part of the microfibrils components. MAGP1 interacts with von Willebrand factor and the active form of TGF-β and BMP. In mice lacking MAGP1, thrombus formation is delayed, increasing the occlusion time of carotid artery despite presenting normal blood coagulation in vitro. MAGP1-containing microfibrils may play a role in hemostasis and thrombosis. In this work, we evaluated the function of MAGP1 and its relation to TGF-β in the arterial thrombosis process.
  
  
  RESULTS
  We analyzed thrombus formation time in wild type and MAGP1-deficient mice comparing Rose Bengal and Ferric Chloride induced arterial lesion. The potential participation of TGF-β in this process was accessed when we treated both wild type and MAGP1-deficient mice with losartan (an antihypertensive drug that decreases TGF-β activity) or captopril (an angiotensin converting enzyme inhibitor that was used as a control antihypertensive drug). Besides, we evaluated thrombus embolization and the gelatinolytic activity in the arterial walls in vitro and ex vivo. Losartan and captopril were able to recover the thrombus formation time without changing blood pressure, activated partial thromboplastin time (aPTT), PT (prothrombin time), platelet aggregation and adhesion, but decreased gelatinase activity.
  
  
  CONCLUSIONS
  Our results suggest that both treatments are effective in the prevention of the sub-endothelial ECM degradation, allowing the recovery of normal thrombus formation.
authors.affiliation: Department of Biochemistry and Tissue Biology, State University of Campinas, SP, Brazil.
authors.forename: Tallita
authors.initials: T
authors.lastname: Vassequi-Silva
authors.affiliation: Department of Biochemistry and Tissue Biology, State University of Campinas, SP, Brazil.
authors.forename: Danielle Sousa
authors.initials: DS
authors.lastname: Pereira
authors.affiliation: Department of Biochemistry and Tissue Biology, State University of Campinas, SP, Brazil.
authors.forename: Ana Cláudia C
authors.initials: ACC
authors.lastname: Nery Diez
authors.affiliation: Department of Biochemistry and Tissue Biology, State University of Campinas, SP, Brazil.
authors.forename: Guilherme G
authors.initials: GG
authors.lastname: Braga
authors.affiliation: Department of Structural and Functional Biology, State University of Campinas, SP, Brazil.
authors.forename: Juliana A
authors.initials: JA
authors.lastname: Godoy
authors.affiliation: Department of Pharmacology, State University of Campinas, SP, Brazil.
authors.forename: Camila B
authors.initials: CB
authors.lastname: Mendes
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, ES, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Dos Santos
authors.affiliation: Laboratory of Genetic and Molecular Cardiology, InCor-HC/FMUSP, SP, Brazil.
authors.forename: José E
authors.initials: JE
authors.lastname: Krieger
authors.affiliation: Department of Pharmacology, State University of Campinas, SP, Brazil.
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
authors.affiliation: Department of Genetics and Evolution and Bioagents, State University of Campinas, SP, Brazil.
authors.forename: Fábio T M
authors.initials: FTM
authors.lastname: Costa
authors.affiliation: Department of Structural and Functional Biology, State University of Campinas, SP, Brazil.
authors.forename: Cristina P
authors.initials: CP
authors.lastname: Vicente
authors.affiliation: Department of Biochemistry and Tissue Biology, State University of Campinas, SP, Brazil. Electronic address: cwerneck@unicamp.br.
authors.forename: Claudio C
authors.initials: CC
authors.lastname: Werneck
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003285:Contractile Proteins / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D017353:Gene Deletion; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D000072260:RNA Splicing Factors; D013927:Thrombosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D003285:Contractile Proteins; D016326:Extracellular Matrix Proteins; D000072260:RNA Splicing Factors; D016212:Transforming Growth Factor beta; C016598:microfibrillar protein; D002216:Captopril; D018093:Gelatinases; D019808:Losartan
keywords: Antihypertensive drugs; Arterial thrombosis; Extracellular matrix; Matrix metalloproteinases; Microfibril-associated glycoprotein; Transforming growth factor-β