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Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany
INHIBITORY POTENTIAL OF NATURAL PEPTIDES ON MATRIX METALLOPROTEINASES (MMPS) IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS(HUVEC)
Abstract number: P210
Kopaliani1 *I., Martin1 M., Deussen1 A.
1TU Dresden, MTZ, Institute of Physiology, Dresden, Germany
The matrix metalloproteinases (MMPs) are zinc dependent enzymes, that control extracellular matrix homeostasis. MMP-2 activity is critical for myocardial and vascular remodeling during hypertension. It is known that Angiotensin II (ANGII) increases MMP-2 expression in human umbilical vein endothelial cells (HUVECs) via tumor necrosis factor alpha (TNF-a); In the present study we revealed the signaling mechanism behind this effect and tested whether the highly potent (IC50= 0.7 mM in HUVEC) ACE-inhibitor isoleucine-tryptophan (IW), a dipeptide found in whey products, exerts direct or indirect inhibitory effect on MMP-2 in HUVEC.
Methods:
One group of HUVECs were only treated with ANGII, ANGI or TNF-a; the second group was pretreated with anti-TNF-a neutralizing antibody before treatment with ANGII, ANGI or TNF-a; the last group of treated cells were cotreated with IW, Captopril (CA) or angiotensine type 1 (AT1) receptor blocker (ARB) Losartan. Inhibitory effects on MMP-2 were studied using gelatin zymography and western blot.
Results:
ANGII, ANGI and TNF-a significantly (>2.5 fold) increased MMP-2 expression in HUVEC. The effect was inhibited (>85%) by pretreatment of the cells with anti-TNF-a neutralizing antibody. IW and CA specifically inhibited (>70%) the ANGI effect on MMP-2 expression; both ANGII and ANGI increased MMP-2 expression was inhibited (>75%) by Losartan. Inhibition of JNK, ERK but not p38 MAP kinases in ANGII, ANGI or TNF-a treated cells resulted in significantly (~90%) decreased MMP-2 expression in HUVEC.
Conclusion:
ANGII and ANGI increase MMP-2 expression in HUVEC via TNF-a signaling and further through JNK and ERK MAP kinases. IW is a potent indirect MMP inhibitor. There appears no direct inhibitory effect of CA and IW on MMP-2 activity.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 204, Supplement 689 :P210