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Uptake of remnant like particles (RLP) in diabetic patients from mouse peritoneal macrophages
1Second Department of Internal Medicine, Gunma University School of Medicine, Japan.
Abstract:
To investigate whether the remnant like particles (RLP), separated from serum by an immunoaffinity gel mixture of anti-apo B-100 and apo A-I monoclonal antibodies, are relevant to the initiation or progression of atherosclerosis, the incorporation of RLP into mouse macrophages was studied using histochemical and biochemical techniques. Remnant lipoproteins such as RLP are reported to contain a large quantity of chyloniron and very low density lipoprotein (VLDL) remnants, especially in diabetic patients. The RLP separated from the sera of 32 diabetic patients were found to be predominantly taken up into macrophages harvested from mouse abdominal cavities by the staining method applying oil red O. Furthermore, using 14C-oleate to prove the uptake of lipoproteins by macrophages, the uptake of RLP-VLDL, a VLDL fraction of RLP by ultracentrifugation, was the next highest to that of the oxidized LDL, which suggests that RLP-VLDL is also aggressively taken up by macrophages. The degree of uptake of RLP-VLDL by macrophages was positively correlated with HbA1c of these diabetic patients (r = 0.556, p < 0.01), irrespective of the ways of the treatment of diabetes. In conclusion, RLP can contribute to the foaming of macrophages, which in turn may explain the acceleration of atherosclerosis in diabetic patients.
Insights
Remnant-like particles (RLP) are readily taken up by macrophages, particularly in diabetic patients. This uptake, especially of RLP-VLDL, correlates with HbA1c and may drive atherosclerosis progression.
Area of Science:
- Cardiovascular Research
- Atherosclerosis Pathogenesis
- Lipid Metabolism
Background:
- Remnant-like particles (RLP) are implicated in atherosclerosis.
- RLP are rich in remnant lipoproteins, especially in diabetic individuals.
- Macrophage foam cell formation is a key event in atherosclerosis.
Purpose of the Study:
- To determine if remnant-like particles (RLP) contribute to atherosclerosis initiation and progression.
- To investigate the uptake of RLP by macrophages.
- To explore the relationship between RLP uptake and diabetic patient characteristics.
Main Methods:
- Immunoaffinity gel separation of RLP using anti-apo B-100 and apo A-I monoclonal antibodies.
- Histochemical staining (Oil Red O) to visualize lipid uptake in macrophages.
- Biochemical assays using 14C-oleate to quantify lipoprotein uptake by macrophages.
- Ultracentrifugation to isolate RLP-VLDL fraction.
Main Results:
- RLP were predominantly taken up by mouse macrophages.
- RLP-VLDL showed significant uptake by macrophages, second only to oxidized LDL.
- Macrophage uptake of RLP-VLDL positively correlated with HbA1c levels in diabetic patients (r = 0.556, p < 0.01).
Conclusions:
- RLP can be incorporated into macrophages, contributing to foam cell formation.
- RLP, particularly RLP-VLDL, may accelerate atherosclerosis in diabetic patients.
- The positive correlation with HbA1c suggests a specific role for RLP in diabetes-associated atherosclerosis.