The inhibitory effect of preeclamptic umbilical cord blood serum on matrix metalloproteinase-1 in arterial slices incubated in vitro.
BACKGROUND
Our previous studies demonstrated that preeclampsia is accompanied by significant alterations in the amounts of peptide growth factors in the umbilical cord serum. Some of these factors (especially IGF-1) are known as regulators of collagen metabolism. The umbilical cord arteries (UCAs) of newborns delivered by mothers with preeclampsia contain more than twice the amount of collagen in comparison to newborns delivered by healthy mothers. A significant role in collagen degradation is attributed to matrix metalloproteinase (MMP)-1 (collagenase 1) and tissue inhibitors of metalloproteinases (TIMPs).


OBJECTIVE
To compare the effects of umbilical cord (UC) blood serum of control and preeclamptic newborns on the content and activity of MMP-1, TIMP-1 and TIMP-2 in UCA wall slices incubated in vitro.


METHODS
Polyacrylamide gel electrophoresis (PAGE) followed by Western immunoblotting allowed to detect MMP-1 as well as TIMP-1 and TIMP-2. The amounts of MMP-1, TIMP-1 and TIMP-2 in UCA slices were measured by immunoenzymatic method (ELISA). MMP-1 activity in the arterial wall was measured using a collagenase-1-specific substrate.


RESULTS
Western immunoblot analyses detected MMP-1, TIMP-1 and TIMP-2 in the incubation fluids and in extracts from the UCA wall. Both 43- and 55-kDa (a zymogen) bands of MMP-1 were visible. The control UC serum stimulated both the amount as well as actual and potential activities of MMP-1 in the arterial wall in a time-dependent manner. In contrast to controls, the preeclamptic serum did not exert such an effect.


CONCLUSIONS
The small amount and low activity of MMP-1 accompanied by elevated amounts of TIMPs (especially TIMP-1) decelerate the degradation and enhance the accumulation of collagen in the preeclamptic UCA wall.
Galewska
Zofia
Z
Department of Medical Biochemistry, Medical Academy of Białystok, Białystok, Poland.
Romanowicz
Lech
L
Gogiel
Tomasz
T
Jaworski
Stefan
S
Bańkowski
Edward
E
D000328:Adult; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D013997:Time Factors; D046509:Tissue Culture Techniques; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014469:Umbilical Arteries / Q000201:enzymology*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020781:Matrix Metalloproteinase 1