Extracellular matrix-mediated control of aortic smooth muscle cell growth and migration by a combination of ascorbic acid, lysine, proline, and catechins.
Extracellular matrix (ECM) function and structure are severely compromised at atherosclerotic lesion sites, contributing to initiation and progression of the disease. This study investigated whether ECM biological properties would be beneficially affected by exposure to nutrients essential for collagen synthesis and posttranslational modification. Confluent layers of human aortic smooth muscle cells (SMC) grown on collagen substrate were cultured in the presence of the tested compounds for 7 to 10 days. Pretreated cells were removed from the ECM surface by differential treatment and replaced with secondary innocent SMC cultures. Secondary SMC growth rate and invasiveness were assayed in standard growth medium. ECM protein composition was assayed immunochemically. ECM produced in the presence of ascorbic acid reduced SMC proliferation in a dose-dependent manner. Plant-derived phenolic extracts expressed different degrees of SMC growth inhibition when present during ECM production. A combination of selected nutrients had a greater effect than did individual components. The ECM deposited by SMC in the presence of ascorbate, lysine, proline, and green tea catechins inhibited SMC migration rate up to 70%. The ECM produced under conditions of chronic essential nutrient deficiency can support proatherosclerotic SMC behavior. A combination of selected nutrients can counteract these adverse effects stronger than individual components.
Ivanov
Vadim
V
Dr Rath Research Institute, Santa Clara, CA, USA.
Ivanova
Svetlana
S
Roomi
M Waheed
MW
Kalinovsky
Tatiana
T
Niedzwiecki
Aleksandra
A
Rath
Matthias
M
D000596:Amino Acids / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D001205:Ascorbic Acid / Q000494:pharmacology*; D028241:Camellia sinensis / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D056604:Grape Seed Extract; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008239:Lysine / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D044945:Proanthocyanidins / Q000494:pharmacology; D011392:Proline / Q000494:pharmacology
D000596:Amino Acids; D000975:Antioxidants; D001205:Ascorbic Acid; D002392:Catechin; D002809:Chondroitin Sulfates; D024042:Collagen Type I; D024061:Collagen Type III; D024141:Collagen Type IV; D004549:Elastin; D005353:Fibronectins; D005419:Flavonoids; D056604:Grape Seed Extract; D006497:Heparan Sulfate; D007797:Laminin; D008239:Lysine; D010936:Plant Extracts; D044945:Proanthocyanidins; D011392:Proline; C511402:Grape Seed Proanthocyanidins; C024070:pycnogenols