Article

Intracellular lipid accumulation, low-density lipoprotein receptor-related protein expression, and cell survival in vascular smooth muscle cells derived from normal and atherosclerotic human coronaries.

Cardiovascular Research Center, CSIC-ICCC, Hospital de la Sta. Creu i Sant Pau, Barcelona, Spain.
European Journal of Clinical Investigation (impact factor: 3.02). 03/2004; 34(3):182-90. DOI:10.1111/j.1365-2362.2004.01316.x
Source: PubMed

ABSTRACT Vascular smooth muscle cell (VSMC) regulation during atherosclerotic plaque progression is determinant for plaque stability.
To study lipid accumulation, low-density lipoprotein receptor-related protein (LRP) expression, and cell survival in VSMCs isolated from nonatherosclerotic areas (normal VSMCs) and advanced atherosclerotic plaques (plaque-VSMCs) of human coronaries.
Normal or plaque-VSMCs were obtained from the intima by modification of the explant technique.
Aggregated low-density lipoprotein (agLDL) (100 micro g mL(-1)) internalization induced higher intracellular cholesteryl ester (CE) accumulation in plaque-VSMC compared with normal VSMCs (89.28 +/- 6.1 vs. 60.34 +/- 4.1 micro g CE mg(-1) of protein; P < 0.05). This internalization was associated with LRP expression, as plaque-VSMCs show higher levels of LRP mRNA (6.06 +/- 0.55 vs. 3.87 +/- 0.28; P < 0.05) and LRP protein expression than normal VSMCs. However, plaque-VSMCs showed a lower proliferative response than normal VSMCs (6536 +/- 636 vs. 11151 +/- 815 c.p.m. [(3)H]thymidine; P < 0.05) and did not respond to platelet-derived growth factor BB (PDGF-BB) stimulus. In agreement, the Bcl(2)/BAX ratio was significantly lower in plaque-VSMCs compared with normal VSMCs (0.14 +/- 0.05 vs. 0.51 +/- 0.07; P < 0.05) and it was independent of lipid loading.
These results indicate that higher intracellular lipid deposition in plaque-VSMCs is related to higher LRP expression levels. However, LRP-mediated agLDL internalization is not directly related to the reduced survival of plaque-VSMCs.

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Keywords

Aggregated low-density lipoprotein
 
atherosclerotic plaque progression
 
atherosclerotic plaques
 
cell survival
 
explant technique
 
higher intracellular lipid deposition
 
higher LRP expression levels
 
lipid loading
 
low-density lipoprotein receptor-related protein
 
LRP expression
 
LRP mRNA
 
LRP protein expression
 
LRP-mediated agLDL internalization
 
nonatherosclerotic areas
 
plaque stability
 
plaque-VSMC
 
plaque-VSMCs
 
platelet-derived growth factor BB
 
study lipid accumulation
 
Vascular smooth muscle cell