The effects of doxycycline regulation on fibrillar collagen production in long term smooth muscle cell culture.
Published: 2004
Language: eng
Number of pages: 121
Description: Collagen remodeling plays an important role in the pathogenesis of vascular diseases including atherosclerosis and aneurysm. In this study I investigate the effect of doxycycline, a matrix metalloproteinase (MMP) inhibitor, on collagen accumulation by smooth muscle cells (SMCs). A long-term  in vitro ascorbate supplemented SMC-extracellular matrix model system was established. After 2 and 4 weeks, doxycycline increased collagen content (from 3.6 to 5.7 and 7.8 to 10.9 ug/cm2), but did not affect MMP-2 secretion in A10 (a rat embryonic SMC line) and primary rat thoracic aortic SMC cultures. In doxycycline treated primary SMCs, there was an immediate and sustained increase in procollagen alpha 1(I) mRNA level (from 115% to 190% of GAPDH expression). However, the proportion of fibrillar versus non-fibrillar collagen was reduced. Under transmission electron microscopy, the collagen fibers were associated with amorphous aggregates, appeared to be nonassembled collagen monomers. In conclusion, doxycycline is a direct regulator of collagen synthesis by SMCs.
Notes: Advisers:  D. W. Courtman; G. J. Wilson.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 43-03, page: 0830.

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