title: Induction of tissue kallikrein in human carotid atheroma does not lead to kallikrein-kinins pathway activation.
abstract: OBJECTIVE
  The impairment of the tissue kallikrein-kinin system (KKS) may result in atheroma development. To determine the involvement of KKS in pathophysiology of human atherosclerosis, we examined the expression of all components of this system as well as angiotensinogen (another tissue kallikrein (TK) substrate), at messenger ribonucleic acid (mRNA) and protein levels in the human carotid artery with and without atheroma.
  
  
  METHODS
  mRNA levels were compared with semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) between atheroma plaque and intact tissue obtained during carotid endarterectomy in 15 patients. The cellular localization of the transcripts and proteins was analyzed with in situ hybridization and immunohistochemistry. TK activity was measured using chromogenic substrate.
  
  
  RESULTS
  The kininogen mRNA was not detected in carotid wall. The TK mRNA was increased four-fold and TK activity 23-fold in atheroma plaque compared with intact tissue. No difference was observed for B1, B2 receptors, kallistatin, angiotensinogen and protein-kinase G type 1alpha (PK-G) mRNAs. The TK and angiotensinogen transcripts as well as kininogen and angiotensinogen proteins were present in both intimal and medial cells. The kininogen immunoreactivity was weaker in atheroma.
  
  
  CONCLUSIONS
  All KKS components were synthesized in arterial wall except kininogen probably coming from plasma. The absence of PK-G mRNA down-regulation in atheroma suggests that the kallikrein induction does not lead to KKS activation.
authors.affiliation: EA 3740, Faculté de médecine RTH Laennec, rue Guillaume Paradin, 69372 Lyon Cedex 08, France.
authors.forename: Liliana
authors.initials: L
authors.lastname: Legedz
authors.forename: Jacques
authors.initials: J
authors.lastname: Randon
authors.forename: Carmine
authors.initials: C
authors.lastname: Sessa
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Baguet
authors.forename: Patrick
authors.initials: P
authors.lastname: Feugier
authors.forename: Catherine
authors.initials: C
authors.lastname: Cerutti
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Bourdillon
authors.forename: Giampiero
authors.initials: G
authors.lastname: Bricca
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism* / Q000601:surgery; D017536:Carotid Artery, Common / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D004691:Endarterectomy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016234:Kallikrein-Kinin System / Q000502:physiology*; D007704:Kininogens / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020840:Tissue Kallikreins / Q000235:genetics*; D017539:Tunica Intima / Q000378:metabolism; D017540:Tunica Media / Q000378:metabolism
chemical_list: D007704:Kininogens; D000808:Angiotensinogen; D020840:Tissue Kallikreins