NG2 Proteoglycan Ablation Reduces Foam Cell Formation and Atherogenesis via Decreased Low-Density Lipoprotein Retention by Synthetic Smooth Muscle Cells

Zhi Gang She, Yunchao Chang, Hong Bo Pang, Wenlong Han, Hou Zao Chen, Jeffrey W. Smith, William B. Stallcup

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Objectives-Obesity and hyperlipidemia are critical risk factors for atherosclerosis. Because ablation of NG2 proteoglycan in mice leads to hyperlipidemia and obesity, we investigated the impact of NG2 ablation on atherosclerosis in apoE null mice. Approach and Results-Immunostaining indicates that NG2 expression in plaque, primarily by synthetic smooth muscle cells, increases during atherogenesis. NG2 ablation unexpectedly results in decreased (30%) plaque development, despite aggravated obesity and hyperlipidemia. Mechanistic studies reveal that NG2-positive plaque synthetic smooth muscle cells in culture can sequester low-density lipoprotein to enhance foam-cell formation, processes in which NG2 itself plays direct roles. In agreement with these observations, low-density lipoprotein retention and lipid accumulation in the NG2/ApoE knockout aorta is 30% less than that seen in the control aorta. Conclusions-These results indicate that synthetic smooth muscle cell-dependent low-density lipoprotein retention and foam cell formation outweigh obesity and hyperlipidemia in promoting mouse atherogenesis. Our study sheds new light on the role of synthetic smooth muscle cells during atherogenesis. Blocking plaque NG2 or altering synthetic smooth muscle cells function may be promising therapeutic strategies for atherosclerosis.

Original languageEnglish (US)
Pages (from-to)49-59
Number of pages11
JournalArteriosclerosis, thrombosis, and vascular biology
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Keywords

  • atherosclerosis
  • chondroitin sulfate proteoglycan 4
  • foam cells
  • macrophages
  • myocytes
  • smooth muscle

Fingerprint Dive into the research topics of 'NG2 Proteoglycan Ablation Reduces Foam Cell Formation and Atherogenesis via Decreased Low-Density Lipoprotein Retention by Synthetic Smooth Muscle Cells'. Together they form a unique fingerprint.

Cite this