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.


OBJECTIVE
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.


METHODS
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.
Llorente-Cortés
V
V
Cardiovascular Research Center, CSIC-ICCC, Hospital de la Sta. Creu i Sant Pau, Barcelona, Spain.
Otero-Viñas
M
M
Berrozpe
M
M
Badimon
L
L
D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002470:Cell Survival; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D002788:Cholesterol Esters; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D012333:RNA, Messenger; D011973:Receptors, LDL