Induction of tissue kallikrein in human carotid atheroma does not lead to kallikrein-kinins pathway activation.
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.
Legedz
Liliana
L
EA 3740, Faculté de médecine RTH Laennec, rue Guillaume Paradin, 69372 Lyon Cedex 08, France.
Randon
Jacques
J
Sessa
Carmine
C
Baguet
Jean-Philippe
JP
Feugier
Patrick
P
Cerutti
Catherine
C
Bourdillon
Marie-Claude
MC
Bricca
Giampiero
G
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
D007704:Kininogens; D000808:Angiotensinogen; D020840:Tissue Kallikreins