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Regulation of L-arginine transport and metabolism in vascular smooth muscle cells

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Abstract

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 grwoth 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.

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  1. Departments of Medicine and Pharmacology, Baylor College of Medicine, 77030, Houston, TX

    William Durante PhD

  2. VA Medical Center, Bldg 109, Rm 130, 2002 Holcombe Blvd., 77030, Houston, TX

    William Durante PhD

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Durante, W. Regulation of L-arginine transport and metabolism in vascular smooth muscle cells. Cell Biochem Biophys 35, 19–34 (2001). https://doi.org/10.1385/CBB:35:1:19

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