Bioflavonoids effectively inhibit smooth muscle cell-mediated contraction of collagen matrix induced by angiotensin II.
Plant-derived bioflavonoids have been recognized to support arterial wall structural integrity and interfere with a variety of proatherosclerotic stimuli. In this study we tested the effects of bioflavonoids on the contractile activity of cultured human aortic smooth muscle cells (SMC) embedded in a 3-dimensional type I collagen matrix. Collagen I solution mixed with human aortic SMC in 24-well plates were allowed to form gels. Tested compounds were added to the wells, and the gels were set afloat by gentle tapping. Digital photographs of the gels were taken after 24 hours of incubation at 37 degrees C. The area of contracted gel was measured and expressed as a percentage of the control gel area from 3 or more replicates. Expression of matrix metalloproteinase (MMP-2) in conditioned media was assessed by gel zymography. Different classes of bioflavanoids showed variable efficiency in inhibiting angiotensin II (ATII)-dependent collagen gel contraction by SMCs. An increase in the number of gallate groups per catechin molecule was associated with increased inhibition of angiotensin II-dependent collagen gel contraction by SMC. Antioxidants (N-acetyl cysteine and ascorbic acid) did not inhibit collagen gel contraction. Bioflavonoid inhibition of collagen gel contraction by SMC correlated with inhibition of matrix metalloproteinase-2 expression. Bioflavonoids participate in the regulation of SMC-mediated contraction and have a strong potential in counteracting pathophysiological effects of ATII. Bioflavonoid activity depends on structural characteristics and can be related to extracellular matrix integrity.
Ivanov
V
V
Matthias Rath Research Insititute, 1260 Memorex Drive, Santa Clara, CA, USA.
Roomi
M W
MW
Kalinovsky
T
T
Niedzwiecki
A
A
Rath
M
M
D000804:Angiotensin II / Q000494:pharmacology*; D001011:Aorta; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D024042:Collagen Type I; D005419:Flavonoids; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D020778:Matrix Metalloproteinase 2