Transforming growth factor-beta(1) stimulates L-arginine transport and metabolism in vascular smooth muscle cells: role in polyamine and collagen synthesis. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) contributes to arterial remodeling by stimulating vascular smooth muscle cell (VSMC) growth and collagen synthesis at sites of vascular injury. Because L-arginine is metabolized to growth-stimulatory polyamines and to the essential collagen precursor L-proline, we examined whether TGF-beta(1) regulates the transcellular transport and metabolism of L-arginine by VSMCs. METHODS AND RESULTS: TGF-beta(1) increased L-arginine uptake, and this was associated with a selective increase in cationic amino acid transporter-1 (CAT-1) mRNA. In addition, TGF-beta(1) stimulated L-arginine metabolism by inducing arginase I mRNA and arginase activity. TGF-beta(1) also stimulated L-ornithine catabolism by elevating ornithine decarboxylase (ODC) and ornithine aminotransferase (OAT) activity. TGF-beta(1) markedly increased the capacity of VSMCs to generate the polyamine putrescine and L-proline from extracellular L-arginine. The TGF-beta(1)-mediated increase in putrescine and L-proline production was reversed by methyl-L-arginine, a competitive inhibitor of cationic amino acid transport, or by hydroxy-L-arginine, an arginase inhibitor. Furthermore, the formation of putrescine was inhibited by the ODC inhibitor alpha-difluoromethylornithine, and L-proline generation was blocked by the OAT inhibitor L-canaline. L-Canaline also inhibited TGF-beta(1)-stimulated type I collagen synthesis. CONCLUSIONS: These results demonstrate that TGF-beta(1) stimulates polyamine and L-proline synthesis by inducing the genes that regulate the transport and metabolism of L-arginine. In addition, they show that TGF-beta(1)-stimulated collagen production is dependent on L-proline formation. The ability of TGF-beta(1) to upregulate L-arginine transport and direct its metabolism to polyamines and L-proline may contribute to arterial remodeling at sites of vascular damage.

publication date

  • February 27, 2001

Research

keywords

  • Arginine
  • Muscle, Smooth, Vascular
  • Transforming Growth Factor beta

Identity

Scopus Document Identifier

  • 0035957042

Digital Object Identifier (DOI)

  • 10.1161/01.cir.103.8.1121

PubMed ID

  • 11222476

Additional Document Info

volume

  • 103

issue

  • 8