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Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL
Open accessAbstract
HDL lowers the risk for atherosclerotic cardiovascular disease by promoting cholesterol efflux from macrophage foam cells. However, other antiatherosclerotic properties of HDL are poorly understood. To test the hypothesis that the lipoprotein carries proteins that might have novel cardioprotective activities, we used shotgun proteomics to investigate the composition of HDL isolated from healthy subjects and subjects with coronary artery disease (CAD). Unexpectedly, our analytical strategy identified multiple complement-regulatory proteins and a diverse array of distinct serpins with serine-type endopeptidase inhibitor activity. Many acute-phase response proteins were also detected, supporting the proposal that HDL is of central importance in inflammation. Mass spectrometry and biochemical analyses demonstrated that HDL3 from subjects with CAD was selectively enriched in apoE, raising the possibility that HDL carries a unique cargo of proteins in humans with clinically significant cardiovascular disease. Collectively, our observations suggest that HDL plays previously unsuspected roles in regulating the complement system and protecting tissue from proteolysis and that the protein cargo of HDL contributes to its antiinflammatory and antiatherogenic properties.
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“Unlike HDL from healthy subjects, HDL from patients with CHD, kidney disease or diabetes mellitus have no protective vascular effects or may even cause paradoxical harmful effects [55, 56, 61, 70, 71, 75, 76].”
From HDL cholesterol: reappraisal of its clinical relevance (2017) · cites this paper as [56]
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“A study in human suggests that HDL from subjects with coronary artery disease was selectively enriched in apoE (34).”
BackgroundGenomics and Cardiovascular Drug Development
Plump, A. S., & Lum, P. Y. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.11.050 · Cited by 31
Morvaridzadeh, M., Zoubdane, N., Heshmati, J., Alami, M., Berrougui, H., & Khalil, A. (2024) · Nutrients · doi:10.3390/nu16050653 · Cited by 39
“[49]. studies indicated a relation between HDL and vitamin D-binding protein [51,52], although direct delivery of vitamin D to the liver by HDL has not been conclusively confirmed Studies in mice suggest that treatment with specific carotenoids increases HDL reverse cholesterol transport capacity…”
ResultHDL-C: clinical equipoise and vascular endothelial function
Campbell, S., & Genest, J. J. (2013) · Expert Review of Cardiovascular Therapy · doi:10.1586/erc.13.17 · Cited by 30
Zheng, K. H., Kaiser, Y., van Olden, C. C., Santos, R. D., Dasseux, J., Genest, J. J., Gaudet, D., Westerink, J., Keyserling, C., Verberne, H. J., et al. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.08.004 · Cited by 33
Apolipoprotein A-I modulates HDL particle size in the absence of apolipoprotein A-II
Melchior, J., Street, S. E., Vaisar, T., Hart, R. C., Jerome, W. G., Kuklenyik, Z., Clouet-Foraison, N., Thornock, C., Bedi, S., SHAH, A. S., et al. (2021) · Journal of Lipid Research · doi:10.1016/j.jlr.2021.100099 · Cited by 31
Self-citationMyeloperoxidase-dependent Inactivation of Surfactant Protein D in Vitro and in Vivo
Crouch, E. C., Hirche, T. O., Shao, B., Boxio, R., Wartelle, J., Benabid, R., McDonald, B., Heinecke, J. W., Matalon, S., & Belaaouaj, A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.097048 · Cited by 31
Self-citationStabilization of the active form(s) of human paraoxonase by human phosphate-binding protein
Rochu, D., Chabrière, É., Renault, F., Elias, M. H., Cléry‐Barraud, C., & Masson, P. (2007) · Biochemical Society Transactions · doi:10.1042/bst0351616 · Cited by 31
Söderlund, S., Watanabe, H., Ehnholm, C., Jauhiainen, M., & Taskinen, M. (2010) · Metabolism · doi:10.1016/j.metabol.2010.01.015 · Cited by 31
“More evidence on the importance of apo E distribution between different HDL subfractions comes from the study where cardiovascular patients had apo E–enriched HDL3, although there was no difference in serum HDL-C [28].”
BackgroundMethodLipid assessment, metabolic syndrome and coronary heart disease risk
Arsenault, B. J., Després, J., Stroes, E. S. G., Wareham, N. J., Kastelein, J. J. P., Khaw, K., & Boekholdt, S. M. (2010) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2010.02357.x · Cited by 31
ETC-216 for coronary artery disease
Nicholls, S. J., Uno, K., Kataoka, Y., & Nissen, S. E. (2011) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2011.557061 · Cited by 31
“Finally, proteomic analyses of HDL continue to broaden the scope of proteins that are carried on HDL particles [73].”
BackgroundWu, K., Joffre, C., Li, X., MacVeigh‐Aloni, M., Hom, M., Hwang, J., Ding, C., Gregoire, S., Brétillon, L., Zhong, J. F., et al. (2009) · Experimental Eye Research · doi:10.1016/j.exer.2009.03.020 · Cited by 30
“Thus, cholesterol efflux from acinar cells to HDL may be mediated by Apo-E localized to the basolateral domain of the acinar cells.”
InfluentialLandmesser, U., von Eckardstein, A., Kastelein, J. J. P., Deanfield, J. E., & Lüscher, T. F. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs182 · Cited by 29
“HDL is a highly complex lipoprotein that can scavenge more than 70 proteins, as identified by proteomics analysis (22), and may contain more than 1000 different lipid species with each of them being modifiable.”
BackgroundReproducible Determination of High-Density Lipoprotein Proteotypes
Goetze, S., Frey, K., Rohrer, L., Radosavljevic, S., Krützfeldt, J., Landmesser, U., Bueter, M., Pedrioli, P. G. A., von Eckardstein, A., & Wollscheid, B. (2021) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00429 · Cited by 29
Proteomic Biomarkers of Atherosclerosis
Vivanco, F., Padial, L. R., Dardé, V. M., de la Cuesta, F., Álvarez‐Llamas, G., Diaz-Prieto, N., & Barderas, M. G. (2008) · Biomarker Insights · doi:10.4137/bmi.s488 · Cited by 31
Sofat, R., Casas, J. P., Meena Kumari, B., Talmud, P. J., Ireland, H., Mika Kivimaki, B., Marmot, M. G., Hughes, A. D., Thom, S., Ebrahim, S. B. J., et al. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.07.021 · Cited by 30
“More recently proteomic analyses have demonstrated circulating complement components complex with high-density lipoprotein (HDL-C) cholesterol [18], which is itself inversely associated with cardiovascular disease [19].”
BackgroundLagor, W. R., Fields, D. W., Khetarpal, S. A., Kumaravel, A., Lin, W. Y., Weintraub, N., Wu, K., Hamm‐Alvarez, S. F., Drazul‐Schrader, D., de la Llera-Moya, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031616 · Cited by 30
“Recent proteomics studies have identified over 50 unique proteins as bona fide components of HDL [20,21,22].”
BackgroundHoly, E. W., Besler, C., Reiner, M. F., Camici, G. G., Manz, J., Beer, J. H., Lüscher, T. F., Landmesser, U., & Tanner, F. C. (2014) · Thrombosis and Haemostasis · doi:10.1160/th13-09-0775 · Cited by 31
“Recent proteomic analysis demonstrated significant alterations in the proteome composition between HDL from healthy subjects and the HDL from patients with CHD (34, 35).”
BackgroundSecreted Progranulin Is a Homodimer and Is Not a Component of High Density Lipoproteins (HDL)
Nguyen, A. D., Nguyen, T. A., Cenik, B., Yu, G., Herz, J., Walther, T. C., Davidson, W. S., & Farese, R. V. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.441949 · Cited by 28
“Consistent with our findings, proteomic studies have failed to detect progranulin in human HDL isolated by ultracentrifugation (34) and by gel-filtration followed by a phospholipid binding resin (31).”
ResultYamashita, S., & Matsuzawa, Y. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000332 · Cited by 30
The anti-inflammatory function of high-density lipoprotein in type II diabetes: A systematic review
Lemmers, R. F. H., van Hoek, M., Lieverse, A. G., Verhoeven, A. J. M., Sijbrands, E. J. G., & Mulder, M. T. (2017) · Journal of clinical lipidology · doi:10.1016/j.jacl.2017.03.013 · Cited by 29
Millar, C. L., Norris, G. H., Jiang, C., Kry, J., Vitols, A., Garcia, C., Park, Y., Lee, J., & Blesso, C. N. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201800404 · Cited by 30
Genetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity
Pamir, N., Pan, C., Plubell, D. L., Hutchins, P. M., Tang, C., Wimberger, J., Irwin, A. D., Vallim, T. Q. D. A., Heinecke, J. W., & Lusis, A. J. (2019) · Journal of Lipid Research · doi:10.1194/jlr.m090555 · Cited by 29
“A full list of the proteins with PSMs per biological replicate is presented in supplemental Table S1.”
BackgroundMethodResultInfluentialSelf-citationHigh density lipoprotein and its apolipoprotein-defined subspecies and risk of dementia
Koch, M., DeKosky, S. T., Goodman, M. O., Sun, J., Furtado, J. D., Fitzpatrick, A. L., Mackey, R. H., Cai, T., López, O. L., Kuller, L. H., et al. (2019) · Journal of Lipid Research · doi:10.1194/jlr.p119000473 · Cited by 32
“Males 534 (54) 265 (51) Age (years) 78 (75, 85) 79 (75, 87) APOE Ɛ4 allele carrier 180 (18) 144 (28) Whites 951 (96) 489 (94) Education (years) 14 (10, 20) 14 (8, 20) Current alcohol drinker 257 (50) 528 (54) Current smoking 40 (4) 20 (4) BMI, kg/m(2) 27 (21, 35) 26 (21, 34) Lipid-lowering medication use 267 (27) 160…”
BackgroundHigh-Density Lipoproteins as Homeostatic Nanoparticles of Blood Plasma
Kudinov, V. A., Alekseeva, O. Y., Torkhovskaya, T. I., Baskaev, K. K., Artyushev, R. I., Saburina, I. N., & Markin, S. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228737 · Cited by 29
“The HDL of healthy people comprise C4a, C4b, C9, and vitronectin, while the HDL of patients with coronary artery disorder are enriched in C3 and C4 [54,55].”
BackgroundMarsche, G., Stadler, J. T., Kargl, J., & Holzer, M. (2022) · Antioxidants · doi:10.3390/antiox11030556 · Cited by 30
Active antithrombin glycoforms are selectively physiosorbed on plasma extracellular vesicles
Radeghieri, A., Alacqua, S., Zendrini, A., Previcini, V., Todaro, F., Martini, G., Ricotta, D., & Bergese, P. (2022) · Journal of Extracellular Biology · doi:10.1002/jex2.57 · Cited by 29
“Notably, AT can be defined as a very “sticky” protein since it has also been found attached to the surface of HDLs (Gordon et al., 2010; Vaisar et al., 2007), conferring these lipoproteins a direct role in coagulation that has not yet been investigated, and as protein corona component of…”
BackgroundGkolfinopoulou, C., Stratikos, E., Theofilatos, D., Kardassis, D., Voulgari, P. V., Drosos, A. A., & Chroni, A. (2015) · The Journal of Rheumatology · doi:10.3899/jrheum.141532 · Cited by 31
Dyslipidemia links obesity to early cerebral neurochemical alterations
Haley, A. P., Gonzales, M. M., Tarumi, T., & Tanaka, H. (2013) · Obesity · doi:10.1002/oby.20332 · Cited by 29
“The HDL particle carries over 40 different proteins (42), and we are unable at this point to identify which components may be more directly linked to the observed effects.”
BackgroundPharmacoproteomics: a chess game on a protein field
D’Alessandro, A., & Zolla, L. (2010) · Drug Discovery Today · doi:10.1016/j.drudis.2010.10.002 · Cited by 29
Characterization of serum amyloid A (SAA) in rainbow trout using a new monoclonal antibody
Kania, P. W., Chettri, J. K., & Buchmann, K. (2014) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2014.08.018 · Cited by 29
von Eckardstein, A. (2010) · Expert Review of Cardiovascular Therapy · doi:10.1586/erc.10.6 · Cited by 30
Black, L. L., Srivastava, R., Schoeb, T. R., Moore, R. D., Barnes, S., & Kabarowski, J. H. S. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500806 · Cited by 29
“We reasoned that the absence of an exacerbatory effect of ApoA-I deficiency on autoimmunity in Sle123→ApoA-I mice might be due to compensatory modifications of other major Apos on HDL in the absence of ApoA-I (29, 38).”
BackgroundHDL metabolism in context: looking on the bright side
Watts, G. F., Barrett, P. H. R., & Chan, D. C. (2008) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328306596d · Cited by 30
High-density lipoproteins: Marker of cardiovascular risk and therapeutic target
Toth, P. P., & Davidson, M. H. (2010) · Journal of clinical lipidology · doi:10.1016/j.jacl.2010.08.002 · Cited by 28
Yassine, H. N., Jackson, A., Reaven, P. D., Nedelkov, D., Nelson, R. W., Lau, S. S., & Borchers, C. H. (2014) · Translational Proteomics · doi:10.1016/j.trprot.2014.10.001 · Cited by 28
“HDL isolation by centrifugation was based on a modification of a previously published protocol [13].”
MethodRao, P., Merath, K., Drigalenko, E. I., Jadhav, A. Y. L., KOMOROWSKI, R. A., Goldblatt, M. I., Rohatgi, A. K., Sarzynski, M. A., Gawrieh, S., & Olivier, M. (2018) · Clinical Proteomics · doi:10.1186/s12014-018-9186-0 · Cited by 28
“Our group and others have shown that APOB can be identified as an HDL-associated protein [6, 8, 10].”
Altered HDL proteome predicts incident CVD in chronic kidney disease patients
Shao, B., Mathew, A. V., Thornock, C., Pennathur, S., Kretzler, M., Gipson, D. S., Bitzer, M., Gadegbeku, C. A., Bellovich, K. A., Bhat, Z. Y., et al. (2021) · Journal of Lipid Research · doi:10.1016/j.jlr.2021.100135 · Cited by 29
“These proteins are linked to lipoprotein metabolism, inflammation, protease inhibition, and complement regulation (17), suggesting that this cargo contributes to the anti-inflammatory and antiatherogenic properties of HDL.”
BackgroundSelf-citationLangfelder, P., Castellani, L. W., Zhou, Z., Paul, E., Davis, R. C., Schadt, E. E., Lusis, A. J., Horvath, S., & Mehrabian, M. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.07.014 · Cited by 29
Speciated Human High-Density Lipoprotein Protein Proximity Profiles
Gauthamadasa, K., Rosales, C., Pownall, H. J., Macha, S. F., Jerome, W. G., Huang, R., & Silva, R. A. G. D. (2010) · Biochemistry · doi:10.1021/bi1015452 · Cited by 28
“Although recent studies have identified more than 100 proteins associated with human HDL (14;15), and these HDL-associated proteins have been shown to be subfraction-specific (16), the majority of HDL-proteins comprise of apoA-I (~70%) and apoA-II (~20%) (17).”
BackgroundChang, F.-J., Yuan, H., Hu, X., Ou, Z., Fu, L., Lin, Z., Wang, Z., Wang, S., Zhou, L., Xu, Y.-Q., et al. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.05.015 · Cited by 28
“Some studies demonstrated that there were differences in the properties of HDL between healthy subjects and patients with diseases [10,12–14,23,36–38].”
BackgroundMethodResultCollins, L. A., & Olivier, M. (2010) · Proteome Science · doi:10.1186/1477-5956-8-42 · Cited by 28
“Although these lipoprotein sources are unique, it was our goal to determine whether or not their inherent differences would ultimately affect a quantitative analysis of the LDL and HDL proteomes.”
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Low‐Kam, C., Rhainds, D., Lo, K. S., Barhdadi, A., Boulé, M., Alem, S., Pedneault-Gagnon, V., Rhéaume, É., Dubé, M., Busseuil, D., et al. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.118.009545 · Cited by 28
“To improve statistical power to identify CEC loci, we prioritized 13 genes from literature searches and another 45 genes from proteomic analyses of HDL particles (Methods).(20) For these 58 genes, we retrieved from our meta-analyses, association results for coding variants (missense, nonsense, and essential splice sit…”
MethodHigh-density lipoproteins for therapeutic delivery systems
Mutharasan, R. K., Foit, L., & Thaxton, C. S. (2015) · Journal of Materials Chemistry B · doi:10.1039/c5tb01332a · Cited by 28
Wahab, A. H. A. A., El-Halawany, M. S., Emam, A., Elfiky, A., & Elmageed, Z. Y. A. (2016) · Biomarkers · doi:10.1080/1354750x.2016.1252966 · Cited by 27
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“In the peripheral circulation, clusterin is attached to HDL-particles [11] and has been observed in atherosclerotic lesions [12, 13], where clusterin may prevent low-density lipoprotein (LDL) oxidation by arterial wall cells [14].”
BackgroundHan, J., & Zhang, X. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.653293 · Cited by 28
“Because C3 is the key molecule in the pathway of complement system activation (7), several hypotheses are proposed that C3 plays an important role in lipid metabolism in the pathogenesis of NAFLD (Figure 2): Firstly, C3 is mainly synthesized by hepatocytes and identified to appear in lipoprotein particles such as high…”
BackgroundVyletelová, V., Nováková, M., & Pašková, Ľ. (2022) · Pharmaceuticals · doi:10.3390/ph15101278 · Cited by 30
Kim, H. J., Jeong, S., Oh, Y. H., Park, S. J., Cho, Y., & Park, S. M. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01805-8 · Cited by 30
“[27] The concentration of hemoglobin, haptoglobin, and hemopexin in HDL-C is strongly and positively correlated with lipid hydroperoxide levels.”
BackgroundMerrill, N. J., Davidson, W. S., He, Y., Díaz Ludovico, I., Sarkar, S., Berger, M. R., McDermott, J. E., Van Eldik, L. J., Wilcock, D. M., Monroe, M. E., et al. (2023) · Science Advances · doi:10.1126/sciadv.adi5571 · Cited by 27
Self-citationPage, S. T., Krauss, R. M., Gross, C., Ishida, B. Y., Heinecke, J. W., Tang, C., Amory, J. K., Schaefer, P. M., Cox, C. J., Kane, J. P., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2813 · Cited by 28
“alter HDL protein composition (9), in turn affecting HDL”
BackgroundMethodSelf-citationHDL-C: Does it matter? An update on novel HDL-directed pharmaco-therapeutic strategies
Gadi, R., Amanullah, A. M., & Figueredo, V. M. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.05.052 · Cited by 27
“This sequence of changes means that HDL is heterogeneous in size because of variations in total lipid cargo and in the array of lipoproteins, enzymes, and other functional proteins that can exist on its surface (35).”
BackgroundInteractions of Apolipoprotein A-I with High-Density Lipoprotein Particles
Nguyen, D., Nickel, M., Mizuguchi, C., Saito, H., Lund‐Katz, S., & Phillips, M. C. (2013) · Biochemistry · doi:10.1021/bi400032y · Cited by 27
Excessive centrifugal fields damage high density lipoprotein [S]
Munroe, W. H., Phillips, M. L., & Schumaker, V. N. (2015) · Journal of Lipid Research · doi:10.1194/jlr.m058735 · Cited by 27
Apolipoprotein A1 Forms 5/5 and 5/4 Antiparallel Dimers in Human High-density Lipoprotein
He, Y., Song, H. D., Anantharamaiah, G. M., Palgunachari, M. N., Bornfeldt, K. E., Segrest, J. P., & Heinecke, J. W. (2019) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra118.000878 · Cited by 29
Self-citationRonsein, G. E., Reyes‐Soffer, G., He, Y., Oda, M. N., Ginsberg, H. N., & Heinecke, J. W. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.054528 · Cited by 27
“Selection of HDL Proteins for Quantification—For targeted quantitative analyses by PRM, we selected the 38 most abundant HDL proteins that had been identified previously in at least two different human populations (20, 31, 35)(Table II).”
MethodSelf-citationApolipoproteins and Alzheimer's pathophysiology
Koch, M., DeKosky, S. T., Fitzpatrick, A. L., Furtado, J. D., López, O. L., Kuller, L. H., Mackey, R. H., Hughes, T. M., Mukamal, K. J., & Jensen, M. K. (2018) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.07.001 · Cited by 26
“Beyond its major structural protein component apoA-I, HDL hosts dozens of associated proteins [8].”
BackgroundCardioprotective Properties of HDL: Structural and Functional Considerations
Pappa, E. T., Elisaf, M., Kostara, C. E., Bairaktari, E. T., & Tsimihodimos, V. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190201142321 · Cited by 28
Holzer, M., Ljubojević-Holzer, S., Souza, D. R., Stadler, J. T., Rani, A., Scharnagl, H., Ronsein, G. E., & Marsche, G. (2022) · Journal of Lipid Research · doi:10.1016/j.jlr.2022.100307 · Cited by 26
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Novel Mechanisms of Action of the Biologicals in Rheumatic Diseases
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Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome
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High Density Lipoprotein: Assembly, Structure, Cargo, and Functions
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“Pioneering studies from the Heinecke laboratory have shown that HDL is an extremely dynamic molecule and carries a cargo of proteins [22].”
BackgroundThe pressure of finding human hypertension genes: new tools, old dilemmas
Charchar, F. J., Zimmerli, L., & Tomaszewski, M. (2008) · Journal of Human Hypertension · doi:10.1038/jhh.2008.67 · Cited by 26
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“The composition and biologic properties of HDL particles are markedly heterogeneous [76], and the influence of size, charge, or protein composition of HDL on its pleiotropic atheroprotective effects is poorly understood.”
BackgroundHenderson, C. M., Vaisar, T., & Hoofnagle, A. N. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3524-6_7 · Cited by 26
Self-citationCardiovascular Disease in Diabetes
Bloomgarden, Z. T. (2008) · Diabetes Care · doi:10.2337/dc08-zb06 · Cited by 28
“Chait commented, “HDL is incredibly complicated,” noting the myriad of proteins present in HDL and its many functions beyond that of reverse cholesterol transport, including anti-inflammatory and antioxidant effects as part of the innate immune system, such that approaches to reduce CETP activity may be inherently fla…”
BackgroundHsieh, J.-Y., Chang, C., Huang, M. T.-H., Chang, C., Chen, C.-Y., Shen, M.-Y., Liao, H.-Y., Wang, G., Chen, C., Chen, C., et al. (2013) · Analytical Chemistry · doi:10.1021/ac402516u · Cited by 25
Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies
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“In a study carried out to match the subspecies of LpA-I and LpA-I,A-II to the subspecies of HDL prepared by ultracentrifugation (17), we found that the two distinct subspecies of LpA-I corresponding to HDL[4] and HDL[7] in Fig.”
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Salazar, M. G., Neugebauer, S., Kacprowski, T., Michalik, S., Ahnert, P., Creutz, P., Rosołowski, M., Löffler, M., Bauer, M. W., Suttorp, N., et al. (2019) · Journal of Proteomics · doi:10.1016/j.jprot.2019.103627 · Cited by 25
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“It is a lipid binding protein and a principal component of high density lipoprotein (16, 17), and pathogens bind Vn to acquire protection from complement-mediated lysis (18).”
BackgroundHuman apolipoprotein A-II reduces atherosclerosis in knock-in rabbits
Koike, T., Koike, Y., Yang, D., Guo, Y., Rom, O., Song, J. W., Xu, J., Chen, Y., Wang, Y., Zhu, T., et al. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.11.028 · Cited by 25
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Plasma apolipoprotein O level increased in the patients with acute coronary syndrome
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“…are the key features for the protective role of HDL, as oxidized HDL (oxHDL) and oxidized LDL (oxLDL) have been consistently linked to increased neuronal death (Keller, Hanni, & Kindy, 2000; Keller, Hanni, & Markesbery, 1999; Sugawa, Ikeda, Kushima, Takashima, & Cynshi, 1997; Vaisar et al., 2007).”
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“However, particularly in light of the recent proteomic data (6, 8), it is not understood how these different morphologies might contribute to HDL subspeciation.”
BackgroundLee‐Rueckert, M., & Kovanen, P. T. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32834a3d24 · Cited by 25
The non-receptor tyrosine phosphatase type 14 blocks caveolin-1-enhanced cancer cell metastasis
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“have the potential to impact function and metabolism (9).”
SELDI-TOF mass spectrometry of High-Density Lipoprotein
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BackgroundThematic Review Series: Proteomics. Proteomic analysis of lipid-protein complexes
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“(56) Many of these are not apolipoproteins, and they are generally present at relatively low abundance.”
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“Recently a proteomic study has reported that HDL carries protein families implicated in complement activation, regulation of proteolysis, and acute-phase response [29].”
Background
Metadata
- Authors
- Vaisar, T., Pennathur, S., Green, P. S., Gharib, S. A., Hoofnagle, A. N., Cheung, M. C., Byun, J., Vuletic, S., Kassim, S., Singh, P., Chea, H., Knopp, R. H., Brunzell, J., Geary, R., Chait, A., Zhao, X.-Q., Elkon, K., Marcovina, S., Ridker, P., Oram, J. F., & Heinecke, J. W.
- Affiliations
- University of Washington (US)
- Wake Forest University (US)
- Harvard University (US)
- Corresponding author
- Heinecke, Jay W.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2007-03-01
- Volume
- 117
- Issue
- 3
- Pages
- 746-756
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1804352
- OpenAlex
- W2083315579
- Cited by
- 942
- References
- 70
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 19 · 2023: 25 · 2022: 36 · 2021: 28 · 2020: 35 · 2019: 36 · 2018: 45 · 2017: 31 · 2016: 51 · 2015: 69 · 2014: 58 · 2013: 81 · 2012: 79
- FWCI
- 79.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington (P30ES07033)
- National Institutes of Health (P30ES07033, DK017047)
- National Heart, Lung, and Blood Institute (HL086798, P01HL030086, HL-078527, K08HL074223, HL-57557, HL074223, R01HL086798, R01HL057557, R01HL078527)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK017047, DK 02456, P01DK002456, P30DK017047)
- National Institute of Environmental Health Sciences (P30 ES-07033, P30ES007033)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- HDL cholesterol, HDL proteome, complement regulation, serpins, protease inhibition, anti-inflammatory activity, coronary artery disease, HDL3, apolipoprotein E, acute phase proteins, atherosclerosis, cardiovascular disease
- MeSH terms
- Amino Acid Sequence, Chromatography, Liquid, Complement Activation, Coronary Artery Disease, Humans, Inflammation, Lipoproteins, HDL, Microscopy, Electron, Scanning, Molecular Sequence Data, Peptide Hydrolases, Mass Spectrometry, Proteomics, Lipid Metabolism
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