The double jeopardy of HDL

Navab, Mohamad; Ananthramaiah, G. M.; Reddy, Srinivasa T.; Lenten, Brian J. Van; Ansell, Benjamin J.; Hama, Susan; Hough, Greg; Bachini, Eugene; Grijalva, Víctor; Wagner, Alan C.; Shaposhnik, Zory; Fogelman, Alan M.

doi:10.1080/07853890510007322

Cited by 126 publications

(93 citation statements)

References 20 publications

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“…As shown in Table 1, more sophisticated analysis shows striking abnormalities: Increased VLDL; remnants and intermediate-density lipoproteins (3); prolonged persistence of postprandial chylomicron remnants (4); accumulation of small dense LDL; modification of apolipoproteins by glycation, oxidation, and carbamoylation (5); increased lipoprotein(a) [Lp(a)] (6); and accumulation of noncardioprotective acute-phase HDL (7,8). An interesting proposal was made by Shoji et al (9), who showed that intermediate-density lipoproteins were an independent risk factor for aortic atherosclerosis.…”

Section: Lipid Abnormalities In Renal Diseasementioning

confidence: 99%

Lipid Changes and Statins in Chronic Renal Insufficiency

Ritz

Wanner

2006

Journal of the American Society of Nephrology

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It has been known for a long time that chronic kidney disease (CKD) is associated with dyslipidemia, but the full extent of abnormalities has been appreciated only recently, because routine laboratory tests fail to disclose the entire spectrum of lipid abnormalities. Lipids, particularly HDL cholesterol, are predictive of cardiovascular events, but a paradoxic inverse relation between cholesterol concentration and cardiovascular death has been noted in uremic patients. This currently is thought to be explained by the confounding effect of microinflammation and possibly calcification, but this is not definitely proved. Several retrospective analyses that included patients with mild or moderate CKD documented benefit from lowering of cholesterol by statins. In contrast, the Die Deutsche Diabetes Dialyse (4D) study and a small Scandinavian study failed to show a benefit from lowering of cholesterol by statins in ESRD. Pathomechanistically, it is possible that nonclassical pathomechanisms override statin-sensitive mechanisms as also suggested by the observation that statins fail to reduce carotid intima-media thickening. Although, experimentally, exposure to lipids (particularly oxidized lipids) aggravates progression, data on the effect of statins on progression in patients with CKD are not definite. The most likely explanation is that the impact of numerous confounders obscures their effect on progression. The increase in urinary protein excretion of patients who are treated with statins had been a cause of concern, but the underlying mechanism (i.e. interference with proximal tubular reabsorption of protein) meanwhile has been well documented.

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Section: Lipid Abnormalities In Renal Diseasementioning

confidence: 99%

Lipid Changes and Statins in Chronic Renal Insufficiency

Ritz

Wanner

2006

Journal of the American Society of Nephrology

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“…Several studies have shown that peptides capable of enhancing the protective effects of HDL 3 against inflammation also inhibit atherosclerosis (4). Not all HDL populations exhibit similar biological activities (5). The protective effect of HDL against atherosclerosis is not only dependent on a higher concentration of HDL in the blood but is also dependent on the molecular composition of the HDL.…”

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confidence: 99%

ApoA-I Mimetic Peptides with Differing Ability to Inhibit Atherosclerosis Also Exhibit Differences in Their Interactions with Membrane Bilayers

Handattu

Garber

Horn

et al. 2007

Journal of Biological Chemistry

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Two homologous apoA-I mimetic peptides, 3F-2 and 3F 14 , differ in their in vitro antiatherogenic properties (Epand, R. M., Epand, R. F., Sayer, B. G., Datta, G., Chaddha, M., and Anantharamaiah, G. M. (2004) J. Biol. Chem. 279, 51404 -51414). In the present work, we demonstrate that the peptide 3F-2, which has more potent anti-inflammatory activity in vitro when administered intraperitoneally to female apoE null mice (20 g/mouse/day) for 6 weeks, inhibits atherosclerosis (lesion area 15,800 ؎ 1000 m 2 , n ‫؍‬ 29), whereas 3F 14 does not (lesion area 20,400 ؎ 1000 m 2 , n ‫؍‬ 26) compared with control saline administered (19,900 ؎ 1400 m 2 , n ‫؍‬ 22). Plasma distribution of the peptides differs in that 3F-2 preferentially associates with high density lipoprotein, whereas 3F 14 preferentially associates with apoB-containing particles. After intraperitoneal injection of 14 C-labeled peptides, 3F 14 reaches a higher maximal concentration and has a longer half-time of elimination than 3F-2. A study of the effect of these peptides on the motional and organizational properties of phospholipid bilayers, using several NMR methods, demonstrates that the two peptides insert to different extents into membranes. 3F-2 with aromatic residues at the center of the nonpolar face partitions closer to the phospholipid head group compared with 3F 14 . In contrast, only 3F 14 affects the terminal methyl group of the acyl chain, decreasing the 2 H order parameter and at the same time also decreasing the molecular motion of this methyl group. This dual effect of 3F 14 can be explained in terms of the cross-sectional shape of the amphipathic helix. These results support the proposal that the molecular basis for the difference in the biological activities of the two peptides lies with their different interactions with membranes.

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“…HDL can undergo profound compositional and functional modifications in subjects with a variety of inflammatory and metabolic disorders with acute phase reactions and systemic inflammation, including systemic lupus erythematosus (SLE), CHD and other diseases causing systemic inflammation [6,36].Acute phase response has both quan-titative and qualitative effects on HDL particle [37]. However, the underlying mechanism, which converts the normal HDL to a dysfunctional stage and its involvement in atherosclerosis development, are still unclear.…”

Section: Discussionmentioning

confidence: 99%

Functionally Defective High Density Lipoprotein is Pro-Oxidant: a Deviation from Normal Atheroprotective Character

Sini¹,

Jayakumari

2013

IJNFS

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High-density lipoprotein is a potential life saving antiatherogenic molecule. However, not all HDL is functionally similar, it can become dysfunctional and may increase atherosclerotic risk. At present, it is unknown, which structural alterations of HDL are essential accounting for its defective functionality and the precise pro-atherogenic mechanisms of action. This study is aimed at identification of the possible prevalence of dysfunctional HDL in subjects and its compositional and functional characterization in comparison to that of functional HDL. HDL was isolated from serum by ultracentrifugation and subjected to functional assays. HDL from majority of healthy subjects showed remarkable antioxidant property by inhibiting LDL oxidation. However, in those healthy subjects with systemic oxidative stress and inflammatory response as well as in those with known coronary heart disease, HDL was dysfunctional and promoted LDL oxidation. Dysfunctional HDL was truly pro-oxidant as it induced intracellular reactive oxygen species formation in cultured monocytes/macrophages. Functional deficiency in HDL did not show any association with HDL-cholesterol content. However, its characterization showed an enrichment of triglycerides, phospholipids, lipid peroxides, and diminished activity of paraoxonase-1, compared to functional HDL, which might render the particle dysfunctional and pro-oxidant.This study demonstrates the prevalence of dysfunctional HDL even among healthy subjects, despite normal HDL-C level, and in majority of subjects with known CHD, which is pro-oxidant in nature that might promote vascular inflammation and atherogenesis. The functional assay of HDL could lead to improved predictive accuracy of cardiovascular disease risk associated with circulating HDL.

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The double jeopardy of HDL

Cited by 126 publications

References 20 publications

Lipid Changes and Statins in Chronic Renal Insufficiency

Lipid Changes and Statins in Chronic Renal Insufficiency

ApoA-I Mimetic Peptides with Differing Ability to Inhibit Atherosclerosis Also Exhibit Differences in Their Interactions with Membrane Bilayers

Functionally Defective High Density Lipoprotein is Pro-Oxidant: a Deviation from Normal Atheroprotective Character

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