title: Extracellular modifications of HDL in vivo and the emerging concept of proteolytic inactivation of preβ-HDL.
abstract: OBJECTIVE
  Both quantity and quality of the circulating HDL particle matter for the optimal antiatherogenic potential of HDL. This review summarizes various mechanisms capable of inducing extracellular modifications of HDL and reducing the function of HDL subclasses as cholesterol acceptors. Special emphasis is laid on the proteolytic inactivation of lipid-poor preβ-migrating HDL (preβ-HDL).
  
  
  RESULTS
  HDL particles can undergo functional inactivation in vivo. During atherogenesis, different cell types in the arterial intima release enzymes into the intimal fluid, potentially capable of causing structural and chemical modifications of the various components present in the lipid core or in the polar surface of the HDL particles. Enzymatic oxidation, lipolysis and proteolysis, and nonenzymatic glycosylation are among the HDL modifications that adversely affect HDL functionality. Proteolysis of preβ-HDL by various proteases present in the arterial intima has emerged as a potential mechanism that impairs the efficiency of HDL to promote cholesterol efflux from macrophage foam cells, the mast cell-derived neutral protease chymase being a prime example of such impairment. A paradigm of proteolytic inactivation of preβ-HDL in vivo is emerging.
  
  
  CONCLUSIONS
  Several extracellular enzymes present in the arterial intima may compromise various cardioprotective functions of HDL. Observations on proteolysis of specific lipid-poor HDL subpopulations in vivo constitute the basis for future studies evaluating the actual impact of proteolytic microenvironments on the initiation and progression of atherosclerotic lesions.
authors: Wihuri Research Institute, Helsinki, Finland. miriam.lee@wri.fi
authors: Miriam
authors: M
authors: Lee-Rueckert
authors: Petri T
authors: PT
authors: Kovanen
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D053442:High-Density Lipoproteins, Pre-beta / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL