title: Enhanced extracellular lipid accumulation in acidic environments.
abstract: OBJECTIVE
  Binding of apolipoprotein B-100-containing lipoproteins (VLDL, IDL, and LDL) to proteoglycans and modifications of the lipoproteins, whether bound or unbound, are key processes in atherogenesis. The complex interplay between binding and modification has been studied at neutral pH conditions. It has been demonstrated that during atherogenesis the extracellular pH of the lesions decreases. We summarize findings suggesting that lipoprotein binding and modification are enhanced at acidic pH.
  
  
  RESULTS
  Many enzymes found in the arterial intima, such as secretory sphingomyelinase and cathepsins, are able to hydrolyze lipoproteins in vitro. These enzymes function optimally at slightly acidic pH (pH 5.5-6.5), and are likely to act on lipoproteins optimally in the acidic plaque areas. Also, the ability of human aortic proteoglycans to bind native VLDL, IDL, and LDL is dramatically increased at acidic pH; this binding can be further increased if these apolipoprotein B-100-containing particles are hydrolytically modified.
  
  
  CONCLUSIONS
  Recent in-vitro findings suggest that in areas of atherosclerotic arterial intima where the extracellular pH is decreased, binding of apolipoprotein B-100-containing lipoproteins to proteoglycans and modification of the lipoproteins by acidic enzymes are enhanced. The pH-induced amplification of these processes will lead to enhanced extracellular accumulation of lipoproteins and accelerated progression of the disease.
authors.affiliation: Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland. kati.oorni@wri.fi
authors.forename: Katariina
authors.initials: K
authors.lastname: Oörni
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D053419:Lipoproteins, IDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D010084:Oxidation-Reduction; D010447:Peptide Hydrolases / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011509:Proteoglycans; D008049:Lipase; D010447:Peptide Hydrolases