Lipoprotein subfractions and cardiovascular disease risk

Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
Current opinion in lipidology (Impact Factor: 5.66). 08/2010; 21(4):305-11. DOI: 10.1097/MOL.0b013e32833b7756
Source: PubMed


Subfractions of LDL and HDL defined by differences in particle size and density have been associated to varying degrees with risk of cardiovascular disease (CVD). Assessment of these relationships has been clouded by lack of standardization among the various analytic methodologies as well as the strong correlations of the subfractions with each other and with standard lipid and lipoprotein risk markers. This review summarizes the properties of the major LDL and HDL particle subclasses, and recent evidence linking their measurement with risk of atherosclerosis and CVD.
Several recent studies have shown independent relationships of levels of LDL and HDL-size subclasses to risk of both coronary artery and cerebrovascular disease. However, the two largest studies, employing nuclear magnetic resonance and ion mobility, respectively, did not find evidence that these measurements improved risk assessment compared with standard lipoprotein assays. In the latter study, principal component analysis was used to group multiple subfraction measurements into three distinct and statistically independent clusters that were related both to cardiovascular outcomes and to genotypes that may reflect underlying metabolic determinants.
Although there is as yet inconclusive evidence as to the extent to which LDL and HDL subfraction measurements improve clinical assessment of CVD risk beyond standard lipid risk markers, recent studies suggest that more refined analyses of lipoprotein subspecies may lead to further improvements in CVD risk evaluation and particularly in identification of appropriate targets for therapeutic intervention in individual patients.

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    • "Moreover, HDL particles possess potent biological activities, including antioxidative [5], anti-inflammatory [6], antiapoptotic, and vasodilatory activities [7] [8]. These activities are not necessarily dependent just on the HDL quantity but rather on the HDL quality [9] [10] [11]. The HDL functional and atheroprotective effects are also attributed to its associated enzyme paraoxonase 1 (PON1). "
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    ABSTRACT: Human carotid atherosclerotic plaque is in direct contact with circulatory blood components. Thus, plaque and blood components may affect each other. The current study presents the effects of plaque chloroform:methanol (C:M) extract on the HDL-associated enzyme paraoxnase 1 (PON1). This study is part of our investigation on the mutual effects of the interactions between atherosclerotic lesions and blood components. Recombinant PON1 (rePON1) was incubated with the human carotid plaques C:M extract and PON1 activities were analyzed. Lactonase and paraoxonase activities were elevated due to C: M treatment, by 140 and by 69%, respectively. Analytical chemistry analyses revealed specific phosphatidylcholines (PCs) as the plaque active components. Tryptophan fluorescence quenching assay, together with molecular docking, shows that PON1 activity is enhanced in correlation with the level of PC affinity to PON1. Molecular docking revealed that PCs interact specifically with H-2-PON1 alpha-helix, which together with H1 enzyme alpha-helix links the protein to the HDL surface. These findings are supported by additional results from the PON1 Delta 20 mutant that lack its H1-alpha-helix. Incubation of this mutant with the plaque C:M extract increased PON1 activity by only 20%, much less than the wild-type PON1 that elevated PON1 activity at the same concentration by as much as 95%. Furthermore, as much as the affinity of the enzyme to the PC was augmented, the ability of PON1 to bind to the HDL particle decreased. Finally, PON1 interaction with PC enhance its uptake into the macrophage cytoplasm. In conclusions, Specific lesion phosphatidylcholines (PCs) present in the human carotid plaque significantly enhance PON1 catalytic activities due to their interaction with the enzyme. Such a lesion's PC-PON1 interaction, in turn, competes with HDL PCs and enhances PON1 uptake by macrophage at the expense of PON1 binding to the HDL.
    Free Radical Biology and Medicine 08/2014; 76. DOI:10.1016/j.freeradbiomed.2014.07.036 · 5.74 Impact Factor
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    • "Lipid testing is helpful when limited to those analytes that have been studied in large cohorts like the Framingham study (15). Newer expanded lipid panels, such as those including genetic testing (16,17), additional information about the size or chromatographic mobility of lipoprotein particles (18,19), or additional biochemical or proteomic biomarkers, run afoul of both Rule 1 and Rule 2. In some cases, these tests rely on evidence that is preliminary, limited, proprietary or otherwise insufficient to support widespread utilization, and in other cases these tests may in fact eventually find a place in appropriate lipid panels, but are currently waiting for evidence that shows us where to apply them most effectively. In the case of newborn screening, the calculus as to whether to include a test in a panel is actually fairly simple, as a test must be paired with a treatment that prevents either a disease or the squeal of that disease. "
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    ABSTRACT: Efficiently managing laboratory test utilization requires both ensuring adequate utilization of needed tests in some patients and discouraging superfluous tests in other patients. After the difficult clinical decision is made to define the patients that do and do not need a test, a wealth of interventions are available to the clinician and laboratorian to help guide appropriate utilization. These interventions are collectively referred to here as the utilization management toolbox. Experience has shown that some tools in the toolbox are weak and other are strong, and that tools are most effective when many are used simultaneously. While the outcomes of utilization management studies are not always as concrete as may be desired, what data is available in the literature indicate that strong utilization management interventions are safe and effective measures to improve patient health and reduce waste in an era of increasing financial pressure.
    Biochemia Medica 06/2014; 24(2):223-34. DOI:10.11613/BM.2014.025 · 2.67 Impact Factor
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    • "Such situations occur in both human [14,15] and animal [16,17] populations. In research settings there is high utility in the ability to rapidly screen profiles to identify interesting density subfractions for further compositional characterization [18,19]. Pragmatically, novel methods for lipoprotein analysis are slowly introduced to clinical practice for diagnostic purposes and used in clinical studies for risk assessment using combinations of analytical and statistical methods [18,19]. "
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    ABSTRACT: Background Despite the importance of abnormalities in lipoprotein metabolism in clinical canine medicine, the fact that most previously used methods for lipoprotein profiling are rather laborious and time-consuming has been a major obstacle to the wide clinical application and use of lipoprotein profiling in this species. The aim of the present study was to assess the feasibility of a continuous lipoprotein density profile (CLPDP) generated within a bismuth sodium ethylenediaminetetraacetic acid (NaBiEDTA) density gradient to characterize and compare the lipoprotein profiles of healthy dogs of various breeds, healthy Miniature Schnauzers, and Miniature Schnauzers with primary hypertriacylglycerolemia. A total of 35 healthy dogs of various breeds with serum triacylglycerol (TAG) and cholesterol concentrations within their respective reference intervals were selected for use as a reference population. Thirty-one Miniature Schnauzers with serum TAG and cholesterol concentrations within their respective reference intervals and 31 Miniature Schnauzers with hypertriacylglyceridemia were also included in the study. Results The results suggest that CLPDP using NaBiEDTA provides unique diagnostic information in addition to measurements of serum TAG and cholesterol concentrations and that it is a useful screening method for dogs with suspected lipoprotein metabolism disorders. Using the detailed and continuous density distribution information provided by the CLPDP, important differences in lipoprotein profiles can be detected even among dogs that have serum TAG and cholesterol concentrations within the reference interval. Miniature Schnauzers with serum TAG and cholesterol concentrations within the reference interval had significantly different lipoprotein profiles than dogs of various other breeds. In addition, it was further established that specific lipoprotein fractions are associated with hypertriacylglyceridemia in Miniature Schnauzers. Conclusions The results of the present study suggest that density gradient ultracentrifugation using NaBiEDTA is a useful screening method for the study of lipoprotein profiles in dogs. Therefore, this method could potentially be used for diagnostic purposes for the separation of dogs suspected of having lipoprotein abnormalities from healthy dogs.
    BMC Veterinary Research 03/2013; 9(1):47. DOI:10.1186/1746-6148-9-47 · 1.78 Impact Factor
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