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.

BACKGROUND: Vascular smooth muscle cell (VSMC) regulation during atherosclerotic plaque progression is determinant for plaque stability. AIMS: 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.
DESIGN: Normal or plaque-VSMCs were obtained from the intima by modification of the explant technique.
RESULTS: 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.
CONCLUSIONS: 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.