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Reverse cholesterol transport in diabetes mellitus
E C Quintão1, W L Medina, M Passarelli
1Lipid Metabolism Laboratory (LIM 10), Hospital das Clínicas, The University of São Paulo Medical School, São Paulo, Brazil. lipideq@usp.br
Diabetes/Metabolism Research and Reviews
|August 10, 2000
Summary
Diabetes mellitus (DM) may accelerate atherosclerosis not primarily due to reverse cholesterol transport (RCT) defects, but rather increased uptake of modified lipoproteins. Further research using animal models is needed to clarify the role of RCT in DM-related atherosclerosis.
Area of Science:
- Cardiovascular Science
- Metabolic Disorders
- Lipid Metabolism
Background:
- Premature atherosclerosis is linked to reverse cholesterol transport (RCT) system defects.
- High-density lipoprotein (HDL) subfractions, cholesteryl ester transfer protein (CETP), and lecithin-cholesterol acyl transferase (LCAT) are critical in RCT.
- Atherosclerosis in diabetes mellitus (DM) is debated regarding its primary cause: RCT defects versus arterial cell uptake of modified lipoproteins.
Purpose of the Study:
- To investigate the role of the reverse cholesterol transport (RCT) system in the development of atherosclerosis in diabetes mellitus (DM).
- To clarify the contribution of HDL particle alterations and their cholesterol-removing efficiency in DM-related atherogenesis.
- To address the interpretational challenges of LCAT and CETP roles in DM due to inadequate in vitro measurement methods.
Main Methods:
- Review of epidemiological data and experimental animal models.
- Analysis of plasma concentrations of HDL subfractions, CETP, and LCAT activity.
- Discussion of the limitations of current in vitro measurement techniques for LCAT and CETP in DM.
- Proposal for the use of knock-out or transgenic mouse models.
Main Results:
- Evidence suggests atherosclerosis in DM may be more attributed to increased arterial wall cell uptake of modified apoB-lipoproteins than primary RCT defects.
- While HDL composition and metabolism are altered in DM, leading to diminished in vitro cholesterol removal, definitive in vivo evidence for its atherogenic importance is lacking.
- The roles of LCAT and CETP in RCT in DM are difficult to interpret due to inadequate or misinterpreted in vitro measurement procedures.
Conclusions:
- The primary driver of atherosclerosis in DM may be enhanced uptake of modified lipoproteins, not necessarily a predominant RCT defect.
- Further in vivo validation is required to establish the significance of altered HDL metabolism in DM-driven atherogenesis.
- Development of appropriate animal models (knock-out/transgenic mice) is crucial for investigating the roles of LCAT, CETP, PLTP, and CETP inhibitors in experimental DM atherosclerosis.