Impaired high density lipoprotein antioxidant activity in healthy postmenopausal women

Zago, Valeria; Sanguinetti, Silvia; Brites, Fernando; Berg, Gabriela; Verona, Julián; Basilio, Francisco; Wikinski, Regina; Schreier, Laura

doi:10.1016/j.atherosclerosis.2004.07.011

Cited by 62 publications

(54 citation statements)

References 39 publications

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“…An important indication that a person lacks apoA-I and has too much apoA-II is elevating triglycerides [47]. These findings are in agreement with Zago et al,who reported that that the degree of HDL functional loss correlated with its triglyceride (TG),but not cholesterol, content [48]. HDL lipid composition may be altered in atherogenic dyslipidemia and associated with inflammatotry state.…”

Section: Discussionsupporting

confidence: 81%

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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Section: Discussionsupporting

confidence: 81%

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

Sini¹,

Jayakumari

2013

IJNFS

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“…Such functionally defi cient HDLs are enriched in triglyceride and depleted in cholesteryl ester in normotriglyceridemic low HDL-C phenotype, metabolic syndrome, type 2 diabetes, and postmenopausal women ( 113,114,(135)(136)(137), refl ecting elevated CETP activity ( 112 ). Mechanistically, the correlation between triglyceride enrichment of HDL particles and impairment of antioxidative activity might be accounted for by ineffective reduction of lipid hydroperoxides by Met residues of apoA-I secondary to alterations in the conformation of its central and C-terminal domains ( 60,61 ).…”

Section: Antioxidative Activitymentioning

confidence: 99%

Unraveling the complexities of the HDL lipidome

Kontush

Lhomme

Chapman

2013

Journal of Lipid Research

316

247

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This article is available online at http://www.jlr.org For many years, HDL lipids were predominantly characterized in terms of the content of their major classes, notably phospholipids, unesterifi ed (free) sterols (predominantly cholesterol), cholesteryl esters, and triglycerides. Cholesterol is the most characteristic component of the HDL lipidome as, in the form of HDL-cholesterol, it represents a major independent negative risk factor for cardiovascular disease (see other reviews in this Thematic Series). It is not cholesterol, however, but phospholipids that quantitatively predominate in the HDL lipidome, accounting, together with sphingomyelin (SM), for 40-60 wt% of total lipid, with lesser proportions of cholesteryl esters (30-40%), triglycerides (5-12%), and free cholesterol (5-10%). Structurally, individual HDL lipid classes fulfi ll distinct functions; phospholipids constitute the surface lipid monolayer of HDL, whereas cholesteryl esters and triglycerides form the hydrophobic lipid core. Unesterifi ed sterols are predominantly located to the surface monolayer, partially penetrating the core.Recent technological advances in mass spectrometry (MS) have enabled application of this powerful technique to provide a detailed identifi cation and quantifi cation of individual molecular species of lipids in the framework of the fi eld known as lipidomics. Application of this approach to plasma lipoproteins has revealed complex profi les consisting of hundreds of molecular lipid species that have been quantifi ed in major lipoprotein classes, including HDL (reviewed in Refs. 1-3 High density lipoproteins (HDL) are small, dense, protein-rich particles compared with other plasma lipoprotein classes. Despite the elevated abundance of multiple structural and functional proteins in HDL particles (see other reviews in this Thematic Series), roughly half of total HDL mass is accounted for by lipid components.

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“…Furthermore, total HDL-mediated protection of LDL from oxidation by Cu 2ϩ is compromised in postmenopausal compared with premenopausal women (Zago et al, 2004). This effect is paralleled by decreased plasma levels of HDL-C, elevated HDL levels of TG, and increased HDL oxidability in the postmenopausal group; the two latter parameters are significantly correlated (Zago et al, 2004).…”

mentioning

confidence: 99%

Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis

Kontush¹,

Chapman²

2006

Pharmacol Rev

659

594

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Impaired high density lipoprotein antioxidant activity in healthy postmenopausal women

Cited by 62 publications

References 39 publications

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

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

Unraveling the complexities of the HDL lipidome

Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis

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