[Expression of matrix metalloproteinases and their inhibitors in the internal carotid artery wall in pathological tortuosity].
The principal morphological sign of fibromuscular dysplasia in pathological tortuosity (PT) of the internal carotid artery (ICA) is the fragmentation of elastic fibers that are degraded by matrix metalloproteinases 2 and 9 (MMP-2, MMP-9). Nevertheless, the role of MMPs and their inhibitors in the pathogenesis of ICA PT remains completely unexplored.


OBJECTIVE
to investigate the expression of elastin-degrading MMPs and their inhibitors in the wall of the ICA in PT by immunohistochemistry and confocal laser scanning microscopy.


METHODS
Immunohistochemical examination was made using antibodies to MMP-2, MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2. MMP-9 and TIMP-1 levels were determined by confocal laser scanning microscopy.


RESULTS
Immunohistochemical examination revealed a statistically significant predominance of high concentrations of MMP-2 and MMP-9 and a low level of their inhibitor TIMP-1 in ICA PT, while simultaneous obvious accumulation of both markers was most often identified in the control group (p<0.05). Analysis of MMP-2/TIMP-2 and MMP-9/TIMP-2 ratios showed the prevalence of the simultaneously high expression of both proteins in ICA PT and in the control group too. The similar data were also obtained by confocal microscopy: the control group showed elevated MMP-9 and TIMP-1 expressions and the ICA PT control displayed a high proteinase and low inhibitor levels (p<0.05).


CONCLUSIONS
Elastic fiber fragmentation in ICA PT is due to imbalance between MMPs and their inhibitors; namely, the prevalence of MMP-2 and MMP-9 over their inhibitor TIMP-1, which leads to the degradation of extracellular matrix components, primarily elastin.
Academician B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia.
E M
EM
Paltseva
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology, Saint Petersburg, Russia.
V O
VO
Polyakova
Academician B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia; I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia.
S A
SA
Oskolkova
Academician B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia.
A V
AV
Abramyan
Academician B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia.
A G
AG
Ivanova
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology, Saint Petersburg, Russia.
Yu S
YS
Krylova
Academician B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia; I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia.
A V
AV
Gavrilenko
D000328:Adult; D000368:Aged; D002343:Carotid Artery, Internal / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism*; D054079:Vascular Malformations / Q000378:metabolism / Q000473:pathology*
C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9