Extracellular Matrix-Mediated Control of Aortic Smooth Muscle Growth and Migration by a Combination of Ascorbic Acid, Lysine, Proline, and Catechins

V. Ivanov, S. Ivanova, M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, M. Rath
Journal of Cardiovascular Pharmacology 2007, 50(5): 541-547

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.

Key Words:
aortic smooth muscle cell, extracellular matrix, ascorbic acid, lysine, proline, catechins

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