Proteoglycans synthesized by arterial smooth muscle cells in the presence of transforming growth factor-β1 exhibit increased binding to LDLs

Peter J. Little, Lisa Tannock, Katherine L. Olin, Alan Chait, Thomas N. Wight

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

The "response-to-retention" hypothesis of atherogenesis states that atherogenic lipoproteins, such as low density lipoprotein (LDL), are retained in vessels by proteoglycans and undergo proatherosclerotic modifications. Transforming growth factor (TGF)-β1 has been identified in atherosclerotic vessels and has been shown to stimulate the synthesis of chondroitin sulfate- and dermatan sulfate-containing proteoglycans by arterial smooth muscle cells (ASMCs), but whether it promotes lipid retention has not been addressed. We investigated whether TGF-β1 modulates the biosynthesis of proteoglycans by ASMCs in a manner that promotes binding to LDL. Proteoglycans isolated from TGF-β1-treated ASMCs exhibited enhanced binding to native LDL compared with the binding of proteoglycans isolated from control cultures (Kd 18 μg/mL LDL versus 81 μg/mL LDL, respectively). The increase in proteoglycan-LDL binding caused by TGF-β1 could be attributed primarily to the glycosaminoglycan portion of the proteoglycans, since the glycosaminoglycan chains liberated from the core proteins of these proteoglycans synthesized in the presence of TGF-β1 exhibited increased LDL binding as well. Furthermore, glycosaminoglycan chains initiated on xyloside (an initiator of glycosaminoglycan synthesis) in the presence of TGF-β1 were longer and displayed enhanced binding to LDL compared with the LDL binding of xyloside-initiated glycosaminoglycan chains from control cultures. These results indicate that TGF-β1 promotes LDL-proteoglycan interaction primarily by its effects on the glycosaminoglycan synthetic machinery of the ASMCs. Therefore, this study supports a proatherogenic role for TGF-β1.

Original languageEnglish
Pages (from-to)55-60
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume22
Issue number1
DOIs
StatePublished - 2002

Keywords

  • Glycosaminoglycans
  • Lipoproteins
  • Proteoglycans
  • Smooth muscle cells
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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