2013
DOI: 10.1074/mcp.m113.028134
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Multi-dimensional Co-separation Analysis Reveals Protein–Protein Interactions Defining Plasma Lipoprotein Subspecies

Abstract: The distribution of circulating lipoprotein particles affects the risk for cardiovascular disease (CVD) in humans. Lipoproteins are historically defined by their density, with low-density lipoproteins positively and high-density lipoproteins (HDLs) negatively associated with CVD risk in large populations. However, these broad definitions tend to obscure the remarkable heterogeneity within each class. Evidence indicates that each class is composed of physically (size, density, charge) and compositionally (prote… Show more

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Cited by 67 publications
(68 citation statements)
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“…2A ). Our analysis confi rmed the presence of classical apolipoproteins, complement factors, fi brinogen, serpins, LCAT, and serum paraoxonase/arylesterase 1 (PON1), all of which were previously reported using other HDL isolation methods ( 35,36 ). The protein-specifi c sum-normalized spectral counts (per participant) estimated the relative proportion of protein abundances across the fi ve native gel size fractions.…”
Section: The Hdl Size Fraction Subproteomessupporting
confidence: 76%
“…2A ). Our analysis confi rmed the presence of classical apolipoproteins, complement factors, fi brinogen, serpins, LCAT, and serum paraoxonase/arylesterase 1 (PON1), all of which were previously reported using other HDL isolation methods ( 35,36 ). The protein-specifi c sum-normalized spectral counts (per participant) estimated the relative proportion of protein abundances across the fi ve native gel size fractions.…”
Section: The Hdl Size Fraction Subproteomessupporting
confidence: 76%
“…In more recent work, we separated human plasma using three different separation techniques (gel fi ltration, ion exchange chromatography, and isoelectric focusing) and tracked protein elution patterns across them. The results show that numerous pairs of proteins tend to comigrate across the different separation techniques ( 83 ), suggesting the existence of discrete and stable subparticles. These reports indicate that, although some apolipoproteins and HDL-associated lipid remodeling factors undoubtedly exchange between HDL particles, others clearly do not.…”
Section: Alterations In the Hdl Proteome In Disease Statesmentioning
confidence: 93%
“…Specific proteins may therefore be confined to distinct HDL subpopulations of distinct origin and function, which are differentially distributed across the HDL particle spectrum (Davidson et al 2009). The HDL fraction as a whole therefore appears to represent "a collection of individualised species with distinct functionalities that happen to have similar physicochemical properties" (Shah et al 2013) and are primarily defined by specific protein-protein interactions facilitated by the presence of phospholipid, rather than "a transient ensemble of randomly exchanging proteins" (Gordon et al 2013;Shah et al 2013). …”
Section: Heterogeneity In Hdl Proteinsmentioning
confidence: 99%