Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial...

Area of Science:

• Biochemistry
• Cardiovascular Biology
• Cell Biology

Background:

• Apolipoprotein CIII (apoCIII) is linked to coronary heart disease and metabolic syndrome.
• ApoCIII's role in inhibiting lipoprotein catabolism is known, but its direct impact on atherogenesis in vascular cells is unclear.
• Investigating the direct effects of apoCIII-containing lipoproteins on vascular cell adhesion is crucial.

Purpose of the Study:

• To determine if lipoproteins with or without apoCIII, or apoCIII itself, directly influence the adhesion of monocytes to endothelial cells.
• To elucidate the cellular mechanisms underlying apoCIII-mediated adhesion.

Main Methods:

• Assessed THP-1 cell and human monocyte adhesion to endothelial cells under static and shear flow conditions.
• Utilized VLDL, LDL, and HDL with and without apoCIII, as well as purified apoCIII.
• Investigated the activation of protein kinase C alpha (PKCalpha) and RhoA, and beta1-integrin activation.

Main Results:

• VLDL and LDL containing apoCIII significantly increased THP-1 cell adhesion to endothelial cells.
• Purified apoCIII also enhanced monocyte adhesion, while apoCI, apoCII, and apoE did not.
• ApoCIII-containing lipoproteins and apoCIII activated PKCalpha and RhoA, leading to beta1-integrin activation and increased cell adhesion.
• HDL without apoCIII decreased adhesion, whereas HDL with apoCIII had no effect.

Conclusions:

• Apolipoprotein B (apoB) lipoproteins carrying apoCIII promote monocyte adhesion to endothelial cells.
• This pro-adhesive effect is mediated through PKCalpha and RhoA signaling pathways, activating beta1-integrin.
• ApoCIII directly contributes to atherogenesis by enhancing monocyte adhesion, beyond its role in lipoprotein metabolism.