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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
Author(s) -
LlorenteCortés V.,
OteroViñas M.,
Berrozpe M.,
Badimon L.
Publication year - 2004
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2004.01316.x
Subject(s) - intracellular , vascular smooth muscle , receptor , microbiology and biotechnology , lipoprotein , cell , medicine , low density lipoprotein , chemistry , smooth muscle , ldl receptor , protein expression , endocrinology , biology , cholesterol , biochemistry , gene
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 µg 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 µg 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.