| Mixture Of Natural
Nutrients Reduces Collagen Matrix Contraction Driven By Aortic
Smooth Muscle Cells
V. Ivanov, S. Ivanova, M.W. Roomi, A. Niedzwiecki,
M. Rath
Matthias Rath Research Institute, 1260 Memorex Drive, Santa Clara,
CA 95050
Oral Presentation at: International Academy
of Cardiology, 12th World Heart Congress, New Trends in Research,
Diagnosis, and Treatment Vancouver, B.C., Canada, July 16-19,
2005
Published in: The Journal of Heart Disease;
vol 4(1): 99, Abstract #394
Abstract
Background:
Impaired arterial smooth muscle contractility plays a leading
role in the development of systemic hypertension. Structural changes,
such as occlusive atherosclerotic plaque formation, and functional
changes, such as hormonal disturbances, play roles in pathophysiological
mechanisms of altered arterial contractility.
Objective:
To study the effects of natural nutrients on arterial smooth muscle
tissue contractility.
Methods:
In vitro model of collagen I gel contraction driven by embedded
cultured human aortic smooth muscle cells (SMC). Tested compounds
were evaluated by their effect on gel contraction, as measured
by change in gel area during 24-hour incubation in serum free
medium. Cellular expression of matrix metalloproteinases (MMPs)
was followed by gel zymography.
Results:
Collagen gel contraction driven by SMC was significantly stimulated
by angiotensins I and II. Addition of 17-beta estradiol enhanced
this effect. Accelerated gel contraction was accompanied by elevated
secretion of MMPs into cell culture media. Purified polyphenols,
catechins, and their natural mixture, green tea leaf extract,
counteracted SMC-dependent collagen gel contraction. Addition
of ascorbic acid and amino acids lysine, arginine, cysteine and
proline to green tea extract enhanced gel relaxation effects.
A reduction in gel contraction correlated with decreased MMP expression.
Specific MMP inhibitors added to the culture medium mimicked gel-relaxing
effects.
Conclusion:
Nutrients can effectively counteract angiotensin-mediated excessive
stimulation of arterial tissue contraction. This anti-hypertensive
action is mediated, at least in part, by inhibiting tissue proteases
and extracellular matrix remodeling.
Comment:
Impaired arterial smooth muscle contractility plays a leading
role in the development of systemic hypertension. Structural
changes, such as occlusive atherosclerotic plaque formation,
and functional changes, such as hormonal disturbances, play
roles in pathophysiological mechanisms of altered arterial
contractility. Accelerated gel contraction was accompanied
by elevated secretion of MMPs into cell culture media. We
found that purified polyphenols and catechins counteracted
SMC-dependent collagen gel contraction; this gel relaxation
effect was further enhanced by addition of ascorbic acid and
amino acids lysine, arginine, cysteine and proline to green
tea extract. A reduction in gel contraction correlated with
decreased MMP expression. These results are significant as
they indicated that nutrients can effectively counteract angiotensin-mediated
excessive stimulation of arterial tissue contraction and have
therapeutic potential in hypertension. |
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