Effects of apolipoprotein M in uremic atherosclerosis

Area of Science:

• Cardiovascular Biology
• Renal Disease Research
• Lipid Metabolism

Background:

• Chronic kidney disease (CKD) accelerates atherosclerosis, leading to premature death.
• Apolipoprotein M (apoM) carries sphingosine-1-phosphate (S1P), potentially mediating anti-atherosclerotic effects via HDL.
• The role of apoM/S1P in atherosclerosis, particularly in uremia, remains controversial.

Purpose of the Study:

• To investigate alterations in plasma apoM/S1P concentrations in a uremic setting.
• To determine the impact of apoM overexpression or deficiency on atherosclerosis in Apoe-deficient mice, both with and without induced uremia.

Main Methods:

• Subtotal nephrectomy was performed on Apoe-deficient mice with varying apoM genotypes (wild type, deficient, overexpressing).
• Plasma apoM/S1P levels and atherosclerotic lesion development were assessed.
• Comparisons were made between nephrectomized and non-nephrectomized control groups.

Main Results:

• Uremia increased plasma apoM but not S1P levels.
• ApoM overexpression significantly elevated plasma S1P, while deficiency decreased it.
• ApoM overexpression augmented aortic root atherosclerosis and plasma cholesterol; aortic arch atherosclerosis was unaffected.
• Neither apoM deficiency nor overexpression influenced uremic atherosclerosis.

Conclusions:

• The apoM/S1P complex's role in atherosclerosis is complex and not consistently anti-atherogenic, especially in Apoe-deficient mice.
• This study challenges the established view of the apoM/S1P complex as protective against atherosclerosis in the context of uremia.