Regulation of L-arginine transport and metabolism in vascular smooth muscle cells.
L-Arginine is a semi-essential amino acid that is metabolized to important regulatory molecules. L-Arginine is transported into vascular smooth muscle cells (SMC) by the cationic amino acid transporter (CAT) family of proteins where it is metabolized to nitric oxide (NO), polyamines, or L-proline. Inflammatory mediators, growth factors, and hemodynamic forces stimulate the transport of L-arginine in vascular SMC by inducing CAT gene expression. However, they exert highly specific and divergent regulatory effects on L-arginine metabolism. Inflammatory cytokines induce the expression of inducible NO synthase (iNOS) and direct the metabolism of L-arginine to the antiproliferative gas, NO. In contrast, growth factors stimulate the expression of arginase I and ornithine decarboxylase (ODC) and channel the metabolism of L-arginine to growth stimulatory polyamines. Alternatively, cyclic mechanical strain blocks both iNOS and ODC activity and stimulates arginase I gene expression, directing the metabolism of L-arginine to the formation of L-proline and collagen. Thus, specific biochemical and biophysical stimuli that are found in the circulation regulate the transport and metabolism of L-arginine in vascular SMC. The ability of these physiologically relevant stimuli to upregulate L-arginine transport and generate specific L-arginine metabolites modulates SMC function and may influence the development of vascular disease.
Durante
W
W
Houston VA Medical Center, TX 77030, USA.
D000818:Animals; D001120:Arginine / Q000737:chemistry* / Q000378:metabolism; D001692:Biological Transport; D004730:Endothelium, Vascular / Q000378:metabolism*; D006439:Hemodynamics; D006801:Humans; D008954:Models, Biological; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism*; D011392:Proline / Q000378:metabolism
D001120:Arginine; D011392:Proline