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Different functions of monocyte subsets in familial hypercholesterolemia: potential function of CD14+ CD16+ monocytes

Sandy Mosig1, Knut Rennert, Siegfried Krause

  • 1Molecular Hemostaseology, Friedrich-Schiller-University of Jena, Jena, Germany. sandy.mosig@mti.uni-jena.de

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|November 13, 2008
PubMed

Insights

In hypercholesterolemia, CD14(+)CD16(+) monocytes show increased uptake of oxidized low-density lipoprotein (oxLDL) and enhanced adherence to endothelial cells. These specialized functions are crucial for clearing oxLDL deposits in the vessel wall.

Area of Science:

  • Immunology
  • Cardiovascular Biology

Background:

  • Hypercholesterolemia is characterized by elevated cholesterol levels, contributing to atherosclerosis.
  • Monocytes are key immune cells involved in vascular inflammation and lipid metabolism.

Purpose of the Study:

  • To investigate differential responses of CD14(+)CD16(+) and CD14(++)CD16(-) monocyte subsets to hypercholesterolemia.
  • To elucidate the role of these monocyte subsets in low-density lipoprotein (LDL) uptake and endothelial cell interactions.

Main Methods:

  • Isolation of monocytes from familial hypercholesterolemia (FH) patients and controls.
  • Flow cytometry, LDL uptake assays, adhesion assays, and laser scanning microscopy.
  • Analysis of surface protein expression (CD68, stabilin-1, CD11c) and phagocytosis capacity.

Main Results:

  • CD14(+)CD16(+) monocytes showed increased oxidized LDL (oxLDL) uptake via CD36, while CD14(++)CD16(-) monocytes preferentially took up native LDL (nLDL).
  • FH-CD14(+)CD16(+) monocytes exhibited enhanced expression of CD68, stabilin-1, CD11c, and increased adherence to activated endothelial cells.
  • CD14(+)CD16(+) monocytes demonstrated superior phagocytosis and resistance to oxLDL-induced impairment.

Conclusions:

  • FH-CD14(+)CD16(+) monocytes possess specialized functions for oxLDL uptake at activated endothelial cells.
  • These functions are hypothesized to be critical for clearing oxLDL deposits and apoptotic cells in hyperlipidemic conditions.

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