Elevated expression of PLTP is atherogenic in apolipoprotein E deficient mice

Area of Science:

• Cardiovascular Research
• Lipid Metabolism
• Atherosclerosis Pathogenesis

Background:

• Plasma phospholipid transfer protein (PLTP) is integral to lipoprotein metabolism.
• The precise role of PLTP in atherosclerosis development remains under investigation.
• Apolipoprotein E (ApoE) deficiency is a well-established model for studying atherosclerosis.

Purpose of the Study:

• To investigate the impact of elevated PLTP expression on atherosclerosis in ApoE deficient mice.
• To elucidate the contribution of PLTP in different cell types to atherosclerosis progression.

Main Methods:

• Assessed plasma PLTP activity, cholesterol levels (total and HDL), and atherosclerosis in ApoE deficient mice with varying PLTP expression.
• Utilized bone marrow transplantation models using wild-type, PLTP-overexpressing, and ApoE deficient donor cells into ApoE deficient recipients.

Main Results:

• Overexpression of PLTP in ApoE deficient mice resulted in more than double the atherosclerosis burden and significantly lower HDL cholesterol.
• Bone marrow-derived cells with elevated PLTP expression exacerbated atherosclerosis and reduced HDL cholesterol, even with ApoE proficient cells.
• ApoE deficient bone marrow transplantation led to higher cholesterol but still showed reduced HDL and increased atherosclerosis with elevated PLTP.

Conclusions:

• Elevated PLTP expression consistently promotes diet-induced atherosclerosis in ApoE deficient models.
• Reduced HDL cholesterol levels are a common consequence of elevated PLTP in these atherosclerosis models.
• PLTP's pro-atherogenic effect is evident regardless of the cellular source in ApoE deficient settings.