Nano Research

, Volume 11, Issue 10, pp 5130–5143 | Cite as

High-density lipoprotein mimetic nanotherapeutics for cardiovascular and neurodegenerative diseases

  • Song Ih Ahn
  • Hyun-Ji Park
  • Jiwon Yom
  • Taeyoung Kim
  • YongTae Kim
Review Article


High-density lipoprotein (HDL) serves as a natural nanoparticle with compositional and functional heterogeneity and contributes to the maintenance of lipid metabolism and various biological functions. HDL also transports endogenous microRNAs, vitamins, hormones, and proteins through blood and interstitial fluids to various organs. These unique and diverse features of HDL have encouraged its applications for the transport of therapeutics and diagnostic reagents in the last decade. In this review, we describe the heterogeneous characteristics and biological functions of HDL and highlight HDL mimetic approaches, including apolipoprotein mimetic peptides and reconstituted HDL nanoparticles. Given the potential of HDL as a nanocarrier delivering various therapeutic agents, we discuss the current representative studies of HDL mimetic nanotherapeutics for cardiovascular and neurodegenerative diseases and analyze the current challenges and future perspective.


high-density lipoprotein nanotherapeutic cardiovascular disease neurodegenerative disease 



This work was supported by the National Institutes of Health Director’s New Innovator Award (No. 1DP2HL142050, Y. K.) and the American Heart Association Scientist Development (No. 15SDG25080314, Y. K.).


  1. [1]
    Mahley, R. W.; Innerarity, T. L.; Rall, S. C., Jr.; Weisgraber, K. H. Plasma lipoproteins: Apolipoprotein structure and function. J. Lipid Res. 1984, 25, 1277–1294.Google Scholar
  2. [2]
    Oram, J. F. The cholesterol mobilizing transporter ABCA1 as a new therapeutic target for cardiovascular disease. Trends Cardiovas. Med. 2002, 12, 170–175.CrossRefGoogle Scholar
  3. [3]
    Kontush, A.; Chapman, M. J. Functionally defective highdensity lipoprotein: A new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol. Rev. 2006, 58, 342–374.CrossRefGoogle Scholar
  4. [4]
    Mulder, W. J. M.; van Leent, M. M. T.; Lameijer, M.; Fisher, E. A.; Fayad, Z. A.; Pérez–Medina, C. High–density lipoprotein nanobiologics for precision medicine. Acc. Chem. Res. 2018, 51, 127–137.CrossRefGoogle Scholar
  5. [5]
    Goldbourt, U.; Yaari, S.; Medalie, J. H. Isolated low HDL cholesterol as a risk factor for coronary heart disease mortality: A 21–year follow–up of 8,000 men. Arterioscler. Thromb. Vasc. Biol. 1997, 17, 107–113.CrossRefGoogle Scholar
  6. [6]
    Kontush, A.; Lindahl, M.; Lhomme, M.; Calabresi,L.; Chapman, J. M.; Davidson, W. S. Structure of HDL: Particle subclasses and molecular components. High Density Lipoproteins 2015, 224, 3–51.Google Scholar
  7. [7]
    Deane, R.; Zlokovic, B. V. Role of the blood–brain barrier in the pathogenesis of Alzheimer’s disease. Curr. Alzheimer Res. 2007, 4, 191–197.CrossRefGoogle Scholar
  8. [8]
    Musiek, E. S.; Holtzman, D. M. Three dimensions of the amyloid hypothesis: Time, space and ‘wingmen’. Nat. Neurosci. 2015, 18, 800–806.CrossRefGoogle Scholar
  9. [9]
    Rosenblum, W. I. Why Alzheimer trials fail: Removing soluble oligomeric beta amyloid is essential, inconsistent, and difficult. Neurobiol. Aging 2014, 35, 969–974.CrossRefGoogle Scholar
  10. [10]
    Vitali, C.; Wellington, C. L.; Calabresi, L. HDL and cholesterol handling in the brain. Cardiovasc. Res. 2014, 103, 405–413.CrossRefGoogle Scholar
  11. [11]
    Chetty, P. S.; Nguyen, D.; Nickel, M.; Lund–Katz, S.; Mayne, L.; Englander, S. W.; Phillips, M. C. Comparison of apoA–I helical structure and stability in discoidal and spherical HDL particles by HX and mass spectrometry. J. Lipid Res. 2013, 54, 1589–1597.CrossRefGoogle Scholar
  12. [12]
    Silva, R. A. G. D.; Huang, R.; Morris, J.; Fang, J. W.; Gracheva, E. O.; Ren, G.; Kontush, A.; Jerome, W. G.; Rye, K. A.; Davidson, W. S. Structure of apolipoprotein A–I in spherical high density lipoproteins of different sizes. Proc. Natl. Acad. Sci. USA 2008, 105, 12176–12181.CrossRefGoogle Scholar
  13. [13]
    Franceschini, G. Apolipoprotein function in health and disease: Insights from natural mutations. Eur. J. Clin. Invest. 1996, 26, 733–746.CrossRefGoogle Scholar
  14. [14]
    Li, W. H.; Tanimura, M.; Luo, C. C.; Datta, S.; Chan, L. The apolipoprotein multigene family: Biosynthesis, structure, structure–function relationships, and evolution. J. Lipid Res. 1988, 29, 245–271.Google Scholar
  15. [15]
    Law, A.; Scott, J. A cross–species comparison of the apolipoprotein–B domain that binds to the LDL receptor. J. Lipid Res. 1990, 31, 1109–1120.Google Scholar
  16. [16]
    DeKroon, R. M.; Mihovilovic, M.; Goodger, Z. V.; Robinette, J. B.; Sullivan, P. M.; Saunders, A. M.; Strittmatter, W. J. ApoE genotype–specific inhibition of apoptosis. J. Lipid Res. 2003, 44, 1566–1573.CrossRefGoogle Scholar
  17. [17]
    Mikolasevic, I.; Žutelija, M.; Mavrinac, V.; Orlic, L. Dyslipidemia in patients with chronic kidney disease: Etiology and management. Int. J. Nephrol. Renovasc. Dis. 2017, 10, 35–45.CrossRefGoogle Scholar
  18. [18]
    Cohn, J. S.; Batal, R.; Tremblay, M.; Jacques, H.; Veilleux, L.; Rodriguez, C.; Mamer, O.; Davignon, J. Plasma turnover of HDL apoC–I, apoC–III, and apoE in humans: In vivo evidence for a link between HDL apoC–III and apoA–I metabolism. J. Lipid Res. 2003, 44, 1976–1983.CrossRefGoogle Scholar
  19. [19]
    Kingwell, B. A.; Chapman, M. J.; Kontush, A.; Miller, N. E. HDL–targeted therapies: Progress, failures and future. Nat. Rev. Drug Discov. 2014, 13, 445–464.CrossRefGoogle Scholar
  20. [20]
    Linton, M. F.; Tao, H.; Linton, E. F.; Yancey, P. G. SR–BI: A multifunctional receptor in cholesterol homeostasis and atherosclerosis. Trends Endocrinol. Metab. 2017, 28, 461–472.CrossRefGoogle Scholar
  21. [21]
    Yvan–Charvet, L.; Wang, N.; Tall, A. R. Role of HDL, ABCA1, and ABCG1 transporters in cholesterol efflux and immune responses. Arterioscler. Thromb. Vasc. Biol. 2010, 30, 139–143.CrossRefGoogle Scholar
  22. [22]
    Vaughan, A. M.; Oram, J. F. ABCA1 and ABCG1 or ABCG4 act sequentially to remove cellular cholesterol and generate cholesterol–rich HDL. J. Lipid Res. 2006, 47, 2433–2443.CrossRefGoogle Scholar
  23. [23]
    Rinninger, F.; Heine, M.; Singaraja, R.; Hayden, M.; Brundert, M.; Ramakrishnan, R.; Heeren, J. High density lipoprotein metabolism in low density lipoprotein receptordeficient mice. J. Lipid Res. 2014, 55, 1914–1924.CrossRefGoogle Scholar
  24. [24]
    Galvani, S.; Sanson, M.; Blaho, V. A.; Swendeman, S. L.; Obinata, H.; Conger, H.; Dahlbäck, B.; Kono, M.; Proia, R. L.; Smith, J. D. et al. HDL–bound sphingosine 1–phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation. Sci. Signal. 2015, 8, ra79.CrossRefGoogle Scholar
  25. [25]
    Rhainds, D.; Brissette, L. The role of scavenger receptor class B type I (SR–BI) in lipid trafficking: Defining the rules for lipid traders. Int. J. Biochem. Cell Biol. 2004, 36, 39–77.CrossRefGoogle Scholar
  26. [26]
    Tall, A. R.; Yvan–Charvet, L.; Terasaka, N.; Pagler, T.; Wang, N. HDL, ABC transporters, and cholesterol efflux: Implications for the treatment of atherosclerosis. Cell Metab. 2008, 7, 365–375.CrossRefGoogle Scholar
  27. [27]
    Litvinov, D.; Mahini, H.; Garelnabi, M. Antioxidant and anti–inflammatory role of paraoxonase 1: Implication in arteriosclerosis diseases. N. Am. J. Med. Sci. 2012, 4, 523–532.CrossRefGoogle Scholar
  28. [28]
    Aharoni, S.; Aviram, M.; Fuhrman, B. Paraoxonase 1 (PON1) reduces macrophage inflammatory responses. Atherosclerosis 2013, 228, 353–361.CrossRefGoogle Scholar
  29. [29]
    Speer, T.; Rohrer, L.; Blyszczuk, P.; Shroff, R.; Kuschnerus, K.; Kränkel, N.; Kania, G.; Zewinger, S.; Akhmedov, A.; Shi, Y. et al. Abnormal high–density lipoprotein induces endothelial dysfunction via activation of Toll–like receptor–2. Immunity 2013, 38, 754–768.CrossRefGoogle Scholar
  30. [30]
    Han, C. Y.; Tang, C. R.; Guevara, M. E.; Wei, H.; Wietecha, T.; Shao, B. H.; Subramanian, S.; Omer, M.; Wang, S. R.; O’Brien, K. D. et al. Serum amyloid A impairs the antiinflammatory properties of HDL. J. Clin. Invest. 2016, 126, 266–281.CrossRefGoogle Scholar
  31. [31]
    Röhrl, C.; Stangl, H. HDL endocytosis and resecretion. Biochim. Biophys. Acta 2013, 1831, 1626–1633.CrossRefGoogle Scholar
  32. [32]
    Kowal, R. C.; Herz, J.; Goldstein, J. L.; Esser, V.; Brown, M. S. Low density lipoprotein receptor–related protein mediates uptake of cholesteryl esters derived from apoprotein E–enriched lipoproteins. Proc. Natl. Acad. Sci. USA 1989, 86, 5810–5814.CrossRefGoogle Scholar
  33. [33]
    Mooberry, L. K.; Sabnis, N. A.; Panchoo, M.; Nagarajan, B.; Lacko, A. G. Targeting the SR–B1 receptor as a gateway for cancer therapy and imaging. Front. Pharmacol. 2016, 7, 466.CrossRefGoogle Scholar
  34. [34]
    Rodrigueza, W. V.; Thuahnai, S. T.; Temel, R. E.; Lund–Katz, S.; Phillips, M. C.; Williams, D. L. Mechanism of scavenger receptor class B type I–mediated selective uptake of cholesteryl esters from high density lipoprotein to adrenal cells. J. Biol. Chem. 1999, 274, 20344–20350.CrossRefGoogle Scholar
  35. [35]
    Shahzad, M. M. K.; Mangala, L. S.; Han, H. D.; Lu, C. H.; Bottsford–Miller, J.; Nishimura, M.; Mora, E. M.; Lee, J. W.; Stone, R. L.; Pecot, C. V. et al. Targeted delivery of small interfering RNA using reconstituted high–density lipoprotein nanoparticles. Neoplasia 2011, 13, 309–319.CrossRefGoogle Scholar
  36. [36]
    Zheng, Y.; Liu, Y. Y.; Jin, H. L.; Pan, S. T.; Qian, Y.; Huang, C.; Zeng, Y. X.; Luo, Q. M.; Zeng, M. S.; Zhang, Z. H. Scavenger receptor B1 is a potential biomarker of human nasopharyngeal carcinoma and its growth is inhibited by HDL–mimetic nanoparticles. Theranostics 2013, 3, 477–486.CrossRefGoogle Scholar
  37. [37]
    Zhang, Z. H.; Chen, J.; Ding, L. L.; Jin, H. L.; Lovell, J. F.; Corbin, I. R.; Cao, W. G.; Lo, P. C.; Yang, M.; Tsao, M. S. et al. HDL–mimicking peptide–lipid nanoparticles with improved tumor targeting. Small 2010, 6, 430–437.CrossRefGoogle Scholar
  38. [38]
    Chen, W.; Jarzyna, P. A.; van Tilborg, G. A. F.; Nguyen, V. A.; Cormode, D. P.; Klink, A.; Griffioen, A. W.; Randolph, G. J.; Fisher, E. A.; Mulder, W. J. M. et al. RGD peptide functionalized and reconstituted high–density lipoprotein nanoparticles as a versatile and multimodal tumor targeting molecular imaging probe. FASEB J. 2010, 24, 1689–1699.CrossRefGoogle Scholar
  39. [39]
    Molino, Y.; David, M.; Varini, K.; Jabes, F.; Gaudin, N.; Fortoul, A.; Bakloul, K.; Masse, M.; Bernard, A.; Drobecq, L. et al. Use of LDL receptor–targeting peptide vectors for in vitro and in vivo cargo transport across the blood–brain barrier. FASEB J. 2017, 31, 1807–1827.CrossRefGoogle Scholar
  40. [40]
    Blaho, V. A.; Galvani, S.; Engelbrecht, E.; Liu, C.; Swendeman, S. L.; Kono, M.; Proia, R. L.; Steinman, L.; Han, M. H.; Hla, T. HDL–bound sphingosine–1–phosphate restrains lymphopoiesis and neuroinflammation. Nature 2015, 523, 342–346.CrossRefGoogle Scholar
  41. [41]
    Hatch, F. T.; Lees, R. S. Practical methods for plasma lipoprotein analysis. Adv. Lipid Res. 1968, 6, 1–68.CrossRefGoogle Scholar
  42. [42]
    Havel, R. J.; Eder, H. A.; Bragdon, J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J. Clin. Invest. 1955, 34, 1345–1353.CrossRefGoogle Scholar
  43. [43]
    Patsch, J. R.; Sailer, S.; Kostner, G.; Sandhofer, F.; Holasek, A.; Braunsteiner, H. Separation of the main lipoprotein density classes from human plasma by rate–zonal ultracentrifugation. J. Lipid Res. 1974, 15, 356–366.Google Scholar
  44. [44]
    McVicar, J. P.; Kunitake, S. T.; Hamilton, R. L.; Kane, J. P. Characteristics of human lipoproteins isolated by selectedaffinity immunosorption of apolipoprotein A–I. Proc. Natl. Acad. Sci. USA 1984, 81, 1356–1360.CrossRefGoogle Scholar
  45. [45]
    Okazaki, M.; Hara, I. Analysis of cholesterol in high density lipoprotein subfractions by high performance liquid chromatography. J. Biochem. 1980, 88, 1215–1218.CrossRefGoogle Scholar
  46. [46]
    Lerch, P. G.; Förtsch, V.; Hodler, G.; Bolli, R. Production and characterization of a reconstituted high density lipoprotein for therapeutic applications. Vox Sang. 1996, 71, 155–164.CrossRefGoogle Scholar
  47. [47]
    Bonomo, E. A.; Swaney, J. B. A rapid method for the synthesis of protein–lipid complexes using adsorption chromatography. J. Lipid Res. 1988, 29, 380–384.Google Scholar
  48. [48]
    Foit, L.; Giles, F. J.; Gordon, L. I.; Thaxton, C. S. Synthetic high–density lipoprotein–like nanoparticles for cancer therapy. Expert Rev. Anticancer Ther. 2015, 15, 27–34.CrossRefGoogle Scholar
  49. [49]
    Ganzetti, G. S.; Busnelli, M.; Parolini, C.; Manzini, S.; Dellera, F.; Sirtori, C. R.; Chiesa, G. Apoa–I depletion in chow–fed apoeko mice severely worsens coronary atherosclerosis development. Atherosclerosis 2016, 252, e104.CrossRefGoogle Scholar
  50. [50]
    Van Lenten, B. J.; Wagner, A. C.; Anantharamaiah, G. M.; Navab, M.; Reddy, S. T.; Buga, G. M.; Fogelman, A. M. Apolipoprotein A–I mimetic peptides. Curr. Atheroscler. Rep. 2009, 11, 52–57.CrossRefGoogle Scholar
  51. [51]
    Sviridov, D.; Remaley, A. T. High–density lipoprotein mimetics: Promises and challenges. Biochem. J. 2015, 472, 249–259.CrossRefGoogle Scholar
  52. [52]
    Marrache, S.; Dhar, S. Biodegradable synthetic high–density lipoprotein nanoparticles for atherosclerosis. Proc. Natl. Acad. Sci. USA 2013, 110, 9445–9450.CrossRefGoogle Scholar
  53. [53]
    Zhang, Z. H.; Cao, W. G.; Jin, H. L.; Lovell, J. F.; Yang, M.; Ding, L. L.; Chen, J.; Corbin, I.; Luo, Q. M.; Zheng, G. Biomimetic nanocarrier for direct cytosolic drug delivery. Angew. Chem., Int. Ed. 2009, 48, 9171–9175.CrossRefGoogle Scholar
  54. [54]
    Qin, S.; Kamanna, V. S.; Lai, J. H.; Liu, T.; Ganji, S. H.; Zhang, L.; Bachovchin, W. W.; Kashyap, M. L. Reverse D4F, an apolipoprotein–AI mimetic peptide, inhibits atherosclerosis in ApoE–null mice. J. Cardiovasc. Pharmacol. Ther. 2012, 17, 334–343.CrossRefGoogle Scholar
  55. [55]
    Park, H. J.; Kuai, R.; Jeon, E. J.; Seo, Y.; Jung, Y.; Moon, J. J.; Schwendeman, A.; Cho, S. W. High–density lipoproteinmimicking nanodiscs carrying peptide for enhanced therapeutic angiogenesis in diabetic hindlimb ischemia. Biomaterials 2018, 161, 69–80.CrossRefGoogle Scholar
  56. [56]
    Amar, M. J. A.; D’Souza, W.; Turner, S.; Demosky, S.; Sviridov, D.; Stonik, J.; Luchoomun, J.; Voogt, J.; Hellerstein, M.; Sviridov, D. et al. 5A apolipoprotein mimetic peptide promotes cholesterol efflux and reduces atherosclerosis in mice. J. Pharmacol. Exp. Ther. 2010, 334, 634–641.CrossRefGoogle Scholar
  57. [57]
    Sviridov, D. O.; Andrianov, A. M.; Anishchenko, I. V.; Stonik, J. A.; Amar, M. J. A.; Turner, S.; Remaley, A. T. Hydrophobic amino acids in the hinge region of the 5A apolipoprotein mimetic peptide are essential for promoting cholesterol efflux by the ABCA1 transporter. J. Pharmacol. Exp. Ther. 2013, 344, 50–58.CrossRefGoogle Scholar
  58. [58]
    Datta, G.; White, C. R.; Dashti, N.; Chaddha, M.; Palgunachari, M. N.; Gupta, H.; Handattu, S. P.; Garber, D. W.; Anantharamaiah, G. M. Anti–inflammatory and recycling properties of an apolipoprotein mimetic peptide, Ac–hE18ANH2. Atherosclerosis 2010, 208, 134–141.CrossRefGoogle Scholar
  59. [59]
    Miles, J.; Khan, M.; Painchaud, C.; Lalwani, N.; Drake, S.; Dasseux, J. L. Single–dose tolerability, pharmacokinetics, and cholesterol mobilization in HDL–C fraction following intravenous administration of ETC–642, a 22–mer ApoA–I analogue and phospholipids complex, in atherosclerosis patients. Arterioscler. Thromb. Vasc. Biol. 2004, 24, e19.Google Scholar
  60. [60]
    Di Bartolo, B. A.; Nicholls, S. J.; Bao, S. S.; Rye, K. A.; Heather, A. K.; Barter, P. J.; Bursill, C. The apolipoprotein A–I mimetic peptide ETC–642 exhibits anti–inflammatory properties that are comparable to high density lipoproteins. Atherosclerosis 2011, 217, 395–400.CrossRefGoogle Scholar
  61. [61]
    Sethi, A. A.; Amar, M.; Shamburek, R. D.; Remaley, A. T. Apolipoprotein AI mimetic peptides: Possible new agents for the treatment of atherosclerosis. Curr. Opin. Investig. Drugs 2007, 8, 201–212.Google Scholar
  62. [62]
    Datta, G.; Chaddha, M.; Garber, D. W.; Chung, B. L.; Tytler, E. M.; Dashti, N.; Bradley, W. A.; Gianturco, S. H.; Anantharamaiah, G. M. The receptor binding domain of apolipoprotein E, linked to a model class A amphipathic helix, enhances internalization and degradation of LDL by fibroblasts. Biochemistry 2000, 39, 213–220.CrossRefGoogle Scholar
  63. [63]
    Scanu, A. Binding of human serum high density lipoprotein apoprotein with aqueous dispersions of phospholipids. J. Biol. Chem. 1967, 242, 711–719.Google Scholar
  64. [64]
    Scanu, A.; Cump, E.; Toth, J.; Koga, S.; Stiller, E.; Albers, L. Degradation and reassembly of a human serum high–density lipoprotein. Evidence for differences in lipid affinity among three classes of polypeptide chains. Biochemistry 1970, 9, 1327–1335.Google Scholar
  65. [65]
    van den Elzen, P.; Garg, S.; León, L.; Brigl, M.; Leadbetter, E. A.; Gumperz, J. E.; Dascher, C. C.; Cheng, T. Y.; Sacks, F. M.; Illarionov, P. A. et al. Apolipoprotein–mediated pathways of lipid antigen presentation. Nature 2005, 437, 906–910.CrossRefGoogle Scholar
  66. [66]
    Tall, A. R. Studies on the transfer of phosphatidylcholine from unilamellar vesicles into plasma high density lipoproteins in the rat. J. Lipid Res. 1980, 21, 354–363.Google Scholar
  67. [67]
    Kim, Y.; Fay, F.; Cormode, D. P.; Sanchez–Gaytan, B. L.; Tang, J.; Hennessy, E. J.; Ma, M. M.; Moore, K.; Farokhzad, O. C.; Fisher, E. A. et al. Single step reconstitution of multifunctional high–density lipoprotein–derived nanomaterials using microfluidics. ACS Nano 2013, 7, 9975–9983.CrossRefGoogle Scholar
  68. [68]
    Toth, M. J.; Kim, T.; Kim, Y. Robust manufacturing of lipidpolymer nanoparticles through feedback control of parallelized swirling microvortices. Lab Chip 2017, 17, 2805–2813.CrossRefGoogle Scholar
  69. [69]
    Ahn, J.; Sei, Y. J.; Jeon, N. L.; Kim, Y. Probing the effect of bioinspired nanomaterials on angiogenic sprouting with a microengineered vascular system. IEEE Trans. Nanotechnol. 2018, 17, 393–397.CrossRefGoogle Scholar
  70. [70]
    Sei, Y. J.; Ahn, J.; Kim, T.; Shin, E.; Santiago–Lopez, A. J.; Jang, S. S.; Jeon, N. L.; Jang, Y. C.; Kim, Y. Detecting the functional complexities between high–density lipoprotein mimetics. Biomaterials 2018, 170, 58–69.CrossRefGoogle Scholar
  71. [71]
    Kim, Y. T.; Chung, B. L.; Ma, M. M.; Mulder, W. J. M.; Fayad, Z. A.; Farokhzad, O. C.; Langer, R. Mass production and size control of lipid–polymer hybrid nanoparticles through controlled microvortices. Nano Lett. 2012, 12, 3587–3591.CrossRefGoogle Scholar
  72. [72]
    Sanchez–Gaytan, B. L.; Fay, F.; Lobatto, M. E.; Tang, J.; Ouimet, M.; Kim, Y.; van der Staay, S. E. M.; van Rijs, S. M.; Priem, B.; Zhang, L. F. et al. HDL–mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages. Bioconjug. Chem. 2015, 26, 443–451.CrossRefGoogle Scholar
  73. [73]
    Benjamin, E. J.; Virani, S. S.; Callaway, C. W.; Chang, A. R.; Cheng, S. S.; Chiuve, S. E.; Cushman, M.; Delling, F. N.; Deo, R.; de Ferranti, S. D. et al. Heart disease and stroke statistics—2018 update: A report from the American heart association. Circulation 2018, 137, e67–e492.CrossRefGoogle Scholar
  74. [74]
    Hu, C. M. J.; Fang, R. H.; Wang, K. C.; Luk, B. T.; Thamphiwatana, S.; Dehaini, D.; Nguyen, P.; Angsantikul, P.; Wen, C. H.; Kroll, A. V. et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 2015, 526, 118–121.CrossRefGoogle Scholar
  75. [75]
    Tang, J. N.; Su, T.; Huang, K.; Dinh, P. U.; Wang, Z. G.; Vandergriff, A.; Hensley, M. T.; Cores, J.; Allen, T.; Li, T. S. et al. Targeted repair of heart injury by stem cells fused with platelet nanovesicles. Nat. Biomed. Eng. 2018, 2, 17–26.CrossRefGoogle Scholar
  76. [76]
    Nguyen, M. M.; Carlini, A. S.; Chien, M. P.; Sonnenberg, S.; Luo, C.; Braden, R. L.; Osborn, K. G.; Li, Y. W.; Gianneschi, N. C.; Christman, K. L. Enzyme–responsive nanoparticles for targeted accumulation and prolonged retention in heart tissue after myocardial infarction. Adv. Mater. 2015, 27, 5547–5552.CrossRefGoogle Scholar
  77. [77]
    Korin, N.; Kanapathipillai, M.; Matthews, B. D.; Crescente, M.; Brill, A.; Mammoto, T.; Ghosh, K.; Jurek, S.; Bencherif, S. A.; Bhatta, D. et al. Shear–activated nanotherapeutics for drug targeting to obstructed blood vessels. Science 2012, 337, 738–742.CrossRefGoogle Scholar
  78. [78]
    Michael Gibson, C.; Korjian, S.; Tricoci, P.; Daaboul, Y.; Yee, M.; Jain, P.; Alexander, J. H.; Steg, P. G.; Lincoff, A. M.; Kastelein, J. J. P. et al. Safety and tolerability of CSL112, a reconstituted, infusible, plasma–derived apolipoprotein A–I, after acute myocardial infarction: The AEGIS–I trial (ApoA–I event reducing in ischemic syndromes I). Circulation 2016, 134, 1918–1930.CrossRefGoogle Scholar
  79. [79]
    Hovingh, G. K.; Smits, L. P.; Stefanutti, C.; Soran, H.; Kwok, S.; de Graaf, J.; Gaudet, D.; Keyserling, C. H.; Klepp, H.; Frick, J. et al. The effect of an apolipoprotein A–I–containing high–density lipoprotein–mimetic particle (CER–001) on carotid artery wall thickness in patients with homozygous familial hypercholesterolemia: The Modifying Orphan Disease Evaluation (MODE) study. Am. Heart. J. 2015, 169, 736–742.e1.CrossRefGoogle Scholar
  80. [80]
    Tabet, F.; Vickers, K. C.; Cuesta Torres, L. F.; Wiese, C. B.; Shoucri, B. M.; Lambert, G.; Catherinet, C.; Prado–Lourenco, L.; Levin, M. G.; Thacker, S. et al. HDL–transferred microRNA–223 regulates ICAM–1 expression in endothelial cells. Nat. Commun. 2014, 5, 3292.CrossRefGoogle Scholar
  81. [81]
    Duivenvoorden, R.; Tang, J.; Cormode, D. P.; Mieszawska, A. J.; Izquierdo–Garcia, D.; Ozcan, C.; Otten, M. J.; Zaidi, N.; Lobatto, M. E.; van Rijs, S. M. et al. A statin–loaded reconstituted high–density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation. Nat. Commun. 2014, 5, 3065.CrossRefGoogle Scholar
  82. [82]
    Argraves, K. M.; Gazzolo, P. J.; Groh, E. M.; Wilkerson, B. A.; Matsuura, B. S.; Twal, W. O.; Hammad, S. M.; Argraves, W. S. High density lipoprotein–associated sphingosine 1–phosphate promotes endothelial barrier function. J. Biol. Chem. 2008, 283, 25074–25081.CrossRefGoogle Scholar
  83. [83]
    Nanjee, M. N.; Doran, J. E.; Lerch, P. G.; Miller, N. E. Acute effects of intravenous infusion of ApoA1/phosphatidylcholine discs on plasma lipoproteins in humans. Arterioscler. Thromb. Vasc. Biol. 1999, 19, 979–989.CrossRefGoogle Scholar
  84. [84]
    Tardif, J. C.; Grégoire, J.; L’Allier, P. L.; Ibrahim, R.; Lespérance, J.; Heinonen, T. M.; Kouz, S.; Berry, C.; Basser, R.; Lavoie, M. A. et al. Effects of reconstituted high–density lipoprotein infusions on coronary atherosclerosis: A randomized controlled trial. JAMA 2007, 297, 1675–1682.CrossRefGoogle Scholar
  85. [85]
    Nasr, H.; Torsney, E.; Poston, R. N.; Hayes, L.; Gaze, D. C.; Basser, R.; Thompson, M. M.; Loftus, I. M.; Cockerill, G. W. Investigating the effect of a single infusion of reconstituted high–density lipoprotein in patients with symptomatic carotid plaques. Ann. Vasc. Surg. 2015, 29, 1380–1391.CrossRefGoogle Scholar
  86. [86]
    Easton, R.; Gille, A.; D’Andrea, D.; Davis, R.; Wright, S. D.; Shear, C. A multiple ascending dose study of CSL112, an infused formulation of ApoA–I. J. Clin. Pharmacol. 2014, 54, 301–310.CrossRefGoogle Scholar
  87. [87]
    Krause, B. R.; Remaley, A. T. Reconstituted HDL for the acute treatment of acute coronary syndrome. Curr. Opin. Lipidol. 2013, 24, 480–486.CrossRefGoogle Scholar
  88. [88]
    Tricoci, P.; D’Andrea, D. M.; Gurbel, P. A.; Yao, Z. L.; Cuchel, M.; Winston, B.; Schott, R.; Weiss, R.; Blazing, M. A.; Cannon, L. et al. Infusion of reconstituted high–density lipoprotein, CSL112, in patients with atherosclerosis: Safety and pharmacokinetic results from a phase 2a randomized clinical trial. J. Am. Heart Assoc. 2015, 4, e002171.CrossRefGoogle Scholar
  89. [89]
    Goffinet, M.; Tardy, C.; Bluteau, A.; Boubekeur, N.; Baron, R.; Keyserling, C.; Barbaras, R.; Lalwani, N.; Dasseux, J. L. Anti–atherosclerotic effect of CER–001, an engineered HDL–mimetic, in the high–fat diet–fed LDLr knockout mice. Circulation 2012, 126, A18667.Google Scholar
  90. [90]
    Tardif, J. C.; Ballantyne, C. M.; Barter, P.; Dasseux, J. L.; Fayad, Z. A.; Guertin, M. C.; Kastelein, J. J. P.; Keyserling, C.; Klepp, H.; Koenig, W. et al. Effects of the high–density lipoprotein mimetic agent CER–001 on coronary atherosclerosis in patients with acute coronary syndromes: A randomized trial. Eur. Heart J. 2014, 35, 3277–3286.CrossRefGoogle Scholar
  91. [91]
    Keyserling, C. H.; Hunt, T. L.; Klepp, H. M.; Scott, R. A.; Barbaras, R.; Schwendeman, A.; Lalwani, N.; Dasseux, J. L. CER–001, a synthetic HDL–mimetic, safely mobilizes cholesterol in healthy dyslipidemic volunteers. Circulation 2011, 124, A15525.Google Scholar
  92. [92]
    Vickers, K. C.; Palmisano, B. T.; Shoucri, B. M.; Shamburek, R. D.; Remaley, A. T. MicroRNAs are transported in plasma and delivered to recipient cells by high–density lipoproteins. Nat. Cell. Biol. 2011, 13, 423–433.CrossRefGoogle Scholar
  93. [93]
    Alzheimer’s Association. 2017 Alzheimer’s disease facts and figures. Alzheimers Dement. 2017, 13, 325–373.Google Scholar
  94. [94]
    Stukas, S.; Robert, J.; Wellington, C. L. High–density lipoproteins and cerebrovascular integrity in Alzheimer’s disease. Cell Metab. 2014, 19, 574–591.CrossRefGoogle Scholar
  95. [95]
    Song, Q. X.; Huang, M.; Yao, L.; Wang, X. L.; Gu, X.; Chen, J.; Chen, J.; Huang, J. L.; Hu, Q. Y.; Kang, T. et al. Lipoprotein–based nanoparticles rescue the memory loss of mice with Alzheimer’s disease by accelerating the clearance of amyloid–beta. ACS Nano 2014, 8, 2345–2359.CrossRefGoogle Scholar
  96. [96]
    Huang, M.; Hu, M.; Song, Q. X.; Song, H. H.; Huang, J. L.; Gu, X.; Wang, X. L.; Chen, J.; Kang, T.; Feng, X. Y. et al. GM1–modified lipoprotein–like nanoparticle: Multifunctional nanoplatform for the combination therapy of Alzheimer’s disease. ACS Nano 2015, 9, 10801–10816.CrossRefGoogle Scholar
  97. [97]
    Song, Q. X.; Song, H. H.; Xu, J. R.; Huang, J. L.; Hu, M.; Gu, X.; Chen, J.; Zheng, G.; Chen, H. Z.; Gao, X. L. Biomimetic ApoE–reconstituted high density lipoprotein nanocarrier for blood–brain barrier penetration and amyloid beta–targeting drug delivery. Mol. Pharm. 2016, 13, 3976–3987.CrossRefGoogle Scholar
  98. [98]
    Redondo, S.; Martínez–González, J.; Urraca, C.; Tejerina, T. Emerging therapeutic strategies to enhance HDL function. Lipids Health Dis. 2011, 10, 175.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Song Ih Ahn
    • 1
    • 2
  • Hyun-Ji Park
    • 1
  • Jiwon Yom
    • 1
    • 2
  • Taeyoung Kim
    • 1
  • YongTae Kim
    • 1
    • 2
    • 3
    • 4
  1. 1.George W. Woodruff School of Mechanical EngineeringGeorgia Institute of TechnologyAtlantaUSA
  2. 2.Parker H. Petit Institute for Bioengineering and BioscienceGeorgia Institute of TechnologyAtlantaUSA
  3. 3.Wallace H. Coulter Department of Biomedical EngineeringGeorgia Institute of TechnologyAtlantaUSA
  4. 4.Institute for Electronics and NanotechnologyGeorgia Institute of TechnologyAtlantaUSA

Personalised recommendations