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). 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. Several extr...Continue Reading
Regulation of the concentration of pre beta high-density lipoprotein in normal plasma by cell membranes and lecithin-cholesterol acyltransferase activity
High density lipoprotein loses its effect to stimulate efflux of cholesterol from foam cells after oxidative modification
Pre-beta high density lipoprotein. Unique disposition of apolipoprotein A-I increases susceptibility to proteolysis
Mast cells of two types differing in neutral protease composition in the human aortic intima. Demonstration of tryptase- and tryptase/chymase-containing mast cells in normal intimas, fatty streaks, and the shoulder region of atheromas
Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction
Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques
Chymase in exocytosed rat mast cell granules effectively proteolyzes apolipoprotein AI-containing lipoproteins, so reducing the cholesterol efflux-inducing ability of serum and aortic intimal fluid
High-density lipoprotein 3 physicochemical modifications induced by interaction with human polymorphonuclear leucocytes affect their ability to remove cholesterol from cells
Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures
Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells
Depletion of pre beta 1LpA1 and LpA4 particles by mast cell chymase reduces cholesterol efflux from macrophage foam cells induced by plasma
Matrix metalloproteinases-3, -7, and -12, but not -9, reduce high density lipoprotein-induced cholesterol efflux from human macrophage foam cells by truncation of the carboxyl terminus of apolipoprotein A-I. Parallel losses of pre-beta particles and the high affinity component of efflux.
Chymase bound to heparin is resistant to its natural inhibitors and capable of proteolyzing high density lipoproteins in aortic intimal fluid
Macrophage metalloproteinases degrade high-density-lipoprotein-associated apolipoprotein A-I at both the N- and C-termini
Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol efflux.
Effect of homocysteinylation on human high-density lipoproteins: a correlation with paraoxonase activity
Group V and X secretory phospholipase A(2)s-induced modification of high-density lipoprotein linked to the reduction of its antiatherogenic functions
Depletion of pre-beta-high density lipoprotein by human chymase impairs ATP-binding cassette transporter A1- but not scavenger receptor class B type I-mediated lipid efflux to high density lipoprotein
Endothelial lipase-modified high-density lipoprotein exhibits diminished ability to mediate SR-BI (scavenger receptor B type I)-dependent free-cholesterol efflux
Cysteine protease cathepsin F is expressed in human atherosclerotic lesions, is secreted by cultured macrophages, and modifies low density lipoprotein particles in vitro.
Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease
The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport
Serum amyloid A (SAA) activates human mast cells which leads into degradation of SAA and generation of an amyloidogenic SAA fragment
Mast cell proteases: physiological tools to study functional significance of high density lipoproteins in the initiation of reverse cholesterol transport
15-Lipoxygenase-mediated modification of high-density lipoproteins impairs SR-BI- and ABCA1-dependent cholesterol efflux from macrophages
Haptoglobin genotype is a regulator of reverse cholesterol transport in diabetes in vitro and in vivo
The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin:cholesterol acyltransferase
Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL
Modification of HDL3 by mild oxidative stress increases ATP-binding cassette transporter 1-mediated cholesterol efflux
ApoA-I cleaved by transthyretin has reduced ability to promote cholesterol efflux and increased amyloidogenicity.
Association of cholesteryl ester transfer protein with HDL particles reduces its proteolytic inactivation by mast cell chymase.
New insights into the role of HDL as an anti-inflammatory agent in the prevention of cardiovascular disease
Mild oxidation promotes and advanced oxidation impairs remodeling of human high-density lipoprotein in vitro
Characterization and properties of pre beta-HDL particles formed by ABCA1-mediated cellular lipid efflux to apoA-I.
The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis.
In vivo macrophage-specific RCT and antioxidant and antiinflammatory HDL activity measurements: New tools for predicting HDL atheroprotection
HDL antielastase activity prevents smooth muscle cell anoikis, a potential new antiatherogenic property
Mast cell-dependent proteolytic modification of HDL particles during anaphylactic shock in the mouse reduces their ability to induce cholesterol efflux from macrophage foam cells ex vivo
Regulation of high-density lipoprotein by inflammatory cytokines: establishing links between immune dysfunction and cardiovascular disease
Identification of novel diagnostic serum biomarkers for Chagas' disease in asymptomatic subjects by mass spectrometric profiling
The ability to promote efflux via ABCA1 determines the capacity of serum specimens with similar high-density lipoprotein cholesterol to remove cholesterol from macrophages
Modifying apolipoprotein A-I by malondialdehyde, but not by an array of other reactive carbonyls, blocks cholesterol efflux by the ABCA1 pathway.
Exchange of apolipoprotein A-I between lipid-associated and lipid-free states: a potential target for oxidative generation of dysfunctional high density lipoproteins.
Relative roles of various efflux pathways in net cholesterol efflux from macrophage foam cells in atherosclerotic lesions
Acidic extracellular environments strongly impair ABCA1-mediated cholesterol efflux from human macrophage foam cells
Proteomic characterization of human plasma high density lipoprotein fractionated by gel filtration chromatography
Modulating cholesteryl ester transfer protein activity maintains efficient pre-β-HDL formation and increases reverse cholesterol transport.
Mast cell activation in vivo impairs the macrophage reverse cholesterol transport pathway in the mouse
Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management
Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells.
Mast cells, neovascularization, and microhemorrhages are associated with saccular intracranial artery aneurysm wall remodeling
Longitudinal changes in high-density lipoprotein cholesterol and cardiovascular events in older adults
HDL functionality in reverse cholesterol transport--Challenges in translating data emerging from mouse models to human disease
Development of a new bioactivatable fluorescent probe for quantification of apolipoprotein A-I proteolytic degradation in vitro and in vivo
Chymase released from hypoxia-activated cardiac mast cells cleaves human apoA-I at Tyr192 and compromises its cardioprotective activity.
Carboxyl-Terminal Cleavage of Apolipoprotein A-I by Human Mast Cell Chymase Impairs Its Anti-Inflammatory Properties
The mast cell as a pluripotent HDL-modifying effector in atherogenesis: from in vitro to in vivo significance
Human macrophage cathepsin B-mediated C-terminal cleavage of apolipoprotein A-I at Ser228 severely impairs antiatherogenic capacity
Atherosclerosis Disease Progression
Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.