title: 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.
abstract: 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.
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, Hospital de la Sta. Creu i Sant Pau, Barcelona, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Llorente-Cortés
authors.forename: M
authors.initials: M
authors.lastname: Otero-Viñas
authors.forename: M
authors.initials: M
authors.lastname: Berrozpe
authors.forename: L
authors.initials: L
authors.lastname: Badimon
mesh_terms: 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*
chemical_list: D000199:Actins; D002788:Cholesterol Esters; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D012333:RNA, Messenger; D011973:Receptors, LDL