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Physiological cyclic stretch directs L‐arginine transport and metabolism to collagen synthesis in vascular smooth muscle
Author(s) -
Durante William,
Liao Lan,
Reyna Sylvia V.,
Peyton Kelly J.,
Schafer Andrew I.
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.99-0960com
Subject(s) - arginase , arginine , proline , vascular smooth muscle , chemistry , catabolism , ornithine , nitric oxide , biochemistry , amino acid , metabolism , microbiology and biotechnology , biology , endocrinology , smooth muscle , organic chemistry
Application of cyclic stretch (10% at 1 hertz) to vascular smooth muscle cells (SMC) increased L‐arginine uptake and this was associated with a specific increase in cationic amino acid transporters (CAT‐2) mRNA. In addition, cyclic stretch stimulated L‐arginine metabolism by inducing arginase I mRNA and arginase activity. In contrast, cyclic stretch inhibited the catabolism of L‐arginine to nitric oxide (NO) by blocking inducible NO synthase expression. Exposure of SMC to cyclic stretch markedly increased the capacity of SMC to generate L‐proline from L‐arginine while inhibiting the formation of polyamines. The stretch‐mediated increase in L‐proline production was reversed by methyl‐L‐arginine, a competitive inhibitor of L‐arginine transport, by hydroxy‐L‐arginine, an arginase inhibitor, or by the ornithine aminotransferase inhibitor L‐canaline. Finally, cyclic stretch stimulated collagen synthesis and the accumulation of type I collagen, which was inhibited by L‐canaline. These results demonstrate that cyclic stretch coordinately stimulates L‐proline synthesis by regulating the genes that modulate the transport and metabolism of L‐arginine. In addition, they show that stretch‐stimulated collagen production is dependent on L‐proline formation. The ability of hemodynamic forces to up‐regulate L‐arginine transport and direct its metabolism to L‐proline may play an important role in stabilizing vascular lesions by promoting SMC collagen synthesis.—Durante, W., Liao, L., Reyna, S. V., Peyton, K. J., Schafer, A. I. Physiological cyclic stretch directs L‐arginine transport and metabolism to collagen synthesis in vascular smooth muscle. FASEB J. 14, 1775–1783 (2000)