Archives of Toxicology

, Volume 90, Issue 3, pp 493–511 | Cite as

Role of silver nanoparticles (AgNPs) on the cardiovascular system

  • Carmen GonzalezEmail author
  • Hector Rosas-Hernandez
  • Manuel Alejandro Ramirez-Lee
  • Samuel Salazar-García
  • Syed F. Ali
Review Article


With the advent of nanotechnology, the use and applications of silver nanoparticles (AgNPs) have increased, both in consumer products as well as in medical devices. However, little is known about the effects of these nanoparticles on human health, more specific in the cardiovascular system, since this system represents an important route of action in terms of distribution, bioaccumulation and bioavailability of the different circulating substances in the bloodstream. A collection of studies have addressed the effects and applications of different kinds of AgNPs (shaped, sized, coated and functionalized) in several components of the cardiovascular system, such as endothelial cells, isolated vessels and organs as well as integrative animal models, trying to identify the underlying mechanisms involved in their actions, to understand their implication in the field of biomedicine. The purpose of the present review is to summarize the most relevant studies to date of AgNPs effects in the cardiovascular system and provide a broader picture of the potential toxic effects and exposure risks, which in turn will allow pointing out the directions of further research as well as new applications of these versatile nanomaterials.


Silver nanoparticles Cardiovascular system Endothelium Blood vessels Toxicity 



The authors would like to acknowledge Mr. Daniel Alberto Maldonado-Ortega for his technical and artistic assistance during the realization of the manuscript.

Conflict of interest

The authors have no conflict of interest to declare.


  1. Ahamed M, Alsalhi MS, Siddiqui MKJ (2010) Silver nanoparticle applications and human health. Clin Chim Acta 41(23–24):1841–1848. doi: 10.1016/j.cca.2010.08.016 CrossRefGoogle Scholar
  2. Al Sabti H (2007) Therapeutic angiogenesis in cardiovascular disease. J Cardiothorac Surg 2:49. doi: 10.1186/1749-8090-2-49 PubMedCentralPubMedCrossRefGoogle Scholar
  3. Asgharian B, Price OT (2007) Deposition of ultrafine (NANO) particles in the human lung. Inhalation Toxicol 19(13):1045–1054. doi: 10.1080/08958370701626501 CrossRefGoogle Scholar
  4. Asharani PV, Lian-Wu Y, Gong Z, Valiyaveettil S (2008) Toxicity of silver nanoparticles in zebrafish models. Nanotechnology 19(25):225102. doi: 10.1088/0957-4484/19/25/255102 CrossRefGoogle Scholar
  5. Asharani PV, Lian-Wu Y, Gong Z, Valiyaveettil S (2011) Comparison of the toxicity of silver, gold and platinum nanoparticles in developing zebrafish embryos. Nanotoxicology 5(1):43–54. doi: 10.3109/17435390.2010.489207 PubMedCrossRefGoogle Scholar
  6. Bandyopadhyay D, Baruah H, Gupta B, Sharma S (2012) Silver nano particles prevent platelet adhesion on immobilized fibrinogen. Assoc Clin Biochem India 27(2):164–170. doi: 10.1007/s12291-011-0169-4 CrossRefGoogle Scholar
  7. Barba-de-la-Rosa AP, Barba-Montoya A, Martinez-Cuevas PP, Hernandez-Ledesma B, León-Galvan MF, De-Leon-Rodriguez A, Gonzalez C (2010) Tryptic amaranth glutelin digests induce endothelial nitric oxide production through inhibition of ACE: antihypertensive role of amaranth peptides. Nitric Oxide 23(2):106–111. doi: 10.1016/j.niox.2010.04.006 CrossRefGoogle Scholar
  8. Bednarczyk J, Lukasiuk K (2011) Tight junctions in neurological diseases. Acta Neurobiol Exp 71(4):393–408Google Scholar
  9. Behra R, Sigg L, Clift MJ, Herzog F, Minghetti M, Johnston B, Petri-Fink A, Rothen-Rutishauser B (2013) Bioavailability of silver nanoparticles and ions: from a chemical and biochemical perspective. J R Soc Interface 10(87):20130396. doi: 10.1098/rsif.2013.0396 PubMedCentralPubMedCrossRefGoogle Scholar
  10. Boop SK, Lettieri T (2008) Comparison of four different colorimetric and fluorometric cytotoxicity assays in a zebrafish liver cell line. BioMed Central Pharmacol 8:8–19. doi: 10.1186/1471-2210-8-8 Google Scholar
  11. Brandt O, Mildner M, Egger AE, Groessl M, Rix U, Posch M, Keppler BK, Strupp C, Mueller B, Stingl G (2012) Nanoscalic silver possesses broad-spectrum antimicrobial activities and exhibits fewer toxicological side effects than silver sulfadiazine. Nanomedicine 8(4):478–488. doi: 10.1016/j.nano.2011.07.005 PubMedCrossRefGoogle Scholar
  12. Brouillet S, Hoffmann P, Benharouga M, Salomon A, Schaal JP, Feige JJ, Alfaidy N (2010) Molecular characterization of EG-VEGF-mediated angiogenesis: differential effects on microvascular and macrovascular endothelial cells. Mol Biol Cell 21(16):2832–2843. doi: 10.1091/mbc.E10-01-0059 PubMedCentralPubMedCrossRefGoogle Scholar
  13. Busse R, Fichtner H, Luckhoff A (1988) Hyperpolarization and increased free calcium in acetylcholine-stimulated endothelial cells. Am J Physiol 255(4/2):H965–H969PubMedGoogle Scholar
  14. Carlson C, Hussain SM, Schrand AM, Braydich-Stolle LK, Hess KL, Jones RL, Schlager JJ (2008) Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. J Physiol Biochem 112(43):13608–13619. doi: 10.1021/jp712087m Google Scholar
  15. Cha K, Hong HW, Choi YG, Lee MJ, Park JH, Chae HK, Ryu G, Myung H (2008) Comparison of acute responses of mice livers to short-term exposure to nano-sized or micro-sized silver particles. Biotechnol Lett 30(11):1893–1899. doi: 10.1007/s10529-008-9786-2 PubMedCrossRefGoogle Scholar
  16. Chaloupka K, Malam Y, Seifalian AM (2010) Nanosilver as a new generation of nanoproduct in biomedical applications. Trends Biotechnol 28(11):580–588. doi: 10.1016/j.tibtech.2010.07.006 PubMedCrossRefGoogle Scholar
  17. Chen X, Schluesener HJ (2008) Nanosilver: a nanoproduct in medical application. Toxicol Lett 176(1):1–12. doi: 10.1016/j.toxlet.2007.10.004 PubMedCrossRefGoogle Scholar
  18. Clapp C, Aranda J, Gonzalez C, Jeziorski MC, Martinez-de-la-Escalera G (2006) Vasoinhibins: endogenous regulators of angiogenesis and vascular function. Trends Endocrinol Metab 17(8):301–307. doi: 10.1016/j.tem.2006.08.002 PubMedCrossRefGoogle Scholar
  19. Clapp C, Thebault S, Jeziorski MC, Martinez-De-La-Escalera G (2009) Peptide hormone regulation of angiogenesis. Am Physiol Rev 89(4):1177–1215. doi: 10.1152/physrev.00024.2009 CrossRefGoogle Scholar
  20. Clapp C, Martinez-de-la-Escalera L, Martinez-de-la-Escalera G (2012) Prolactin and blood vessels: a comparative endocrinology perspective. Gen Comp Endocrinol 176(3):336–340. doi: 10.1016/j.ygcen.2011.12.033 PubMedCrossRefGoogle Scholar
  21. Corbacho AM, Martinez-de-la-Escalera G, Clapp C (2002) Roles of prolactin and related members of the prolactin/growth hormone/placental lactogen family in angiogenesis. J Endocrinol 173(2):219–238. doi: 10.1677/joe.0.1730219 PubMedCrossRefGoogle Scholar
  22. Costa CS, Ronconi JV, Daufenbach JF, Gonçalves CL, Rezin GT, Streck EL, Paula MM (2010) In vitro effects of silver nanoparticles on the mitochondrial respiratory chain. Mol Cell Biochem 342(1–2):51–56. doi: 10.1007/s11010-010-0467-9 PubMedCrossRefGoogle Scholar
  23. Cui D, Gao H (2003) Advance and prospect of bionanomaterials. Biotechnol Prog 19(3):683–692. doi: 10.1021/bp025791i PubMedCrossRefGoogle Scholar
  24. Drescher D, Büchner T, McNaughton D, Kneipp J (2013) SERS reveals the specific interaction of silver and gold nanoparticles with hemoglobin and red blood cell components. Phys Chem Chem Phys 15(15):5364–5374. doi: 10.1039/c3cp43883j PubMedCrossRefGoogle Scholar
  25. Español AJ, Goren N, Ribeiro ML, Sales ME (2010) Nitric oxide synthase 1 and cyclooxygenase-2 enzymes are targets of muscarinic activation in normal and inflamed NIH3T3 cells. Inflamm Res 59(3):227–238. doi: 10.1007/s00011-009-0097-4 PubMedCrossRefGoogle Scholar
  26. Espinosa-Cristobal LF, Martinez-Castañon GA, Loyola-Rodriguez JP, Patiño-Marin N, Reyes-Macías JF, Vargas-Morales JM, Ruiz F (2013) Toxicity, distribution, and accumulation of silver nanoparticles in Wistar rats. J Nanopart Res. doi: 10.1007/S11051-013-1702-6 Google Scholar
  27. Farley A, Hendry C, McLafferty E (2013) Blood components. Nurs Stand 27(13):35–42. doi: 10.7748/ns2012. CrossRefGoogle Scholar
  28. Garcia C, Aranda J, Arnold E, Thebault S, Macotela Y, Lopez-Casillas F, Mendoza V, Quiroz-Mercado H, Hernandez-Montiel HL, Lin SH, de-la-Escalera GM, Clapp C (2008) Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A dependent eNOs inactivation. J Clin Investig 118(6):2291–2300. doi: 10.1172/JCI34508 PubMedCentralPubMedGoogle Scholar
  29. Geiser M, Rothen-Rutishauser B, Kapp N, Schürch S, Kreyling W, Schulz H, Semmler M, Im-Hof V, Heyder J, Gehr P (2005) Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ Health Perspect 113(11):1555–1560. doi: 10.1289/ehp.8006 PubMedCentralPubMedCrossRefGoogle Scholar
  30. Ghofrani H, Voswinckel R, Reichenberger F, Olschewski H, Haredza P, Karadaş B, Schermuly RT, Weissmann N, Seeger W, Grimminger F (2004) Differences in hemodynamic and oxygenation response to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension. J Am Coll Cardiol 44(7):1488–1496. doi: 10.1016/j.jacc.2004.06.060 PubMedGoogle Scholar
  31. Gnanadhas DP, Ben Thomas M, Thomas R, Raichur AM, Chakravortty D (2013) Interaction of silver nanoparticles with serum proteins affects their antimicrobial activity in vivo. Antimicrob Agents Chemother 57(10):4945–4955. doi: 10.1128/AAC.00152-13 PubMedCentralPubMedCrossRefGoogle Scholar
  32. Godin BS, Sakamoto JH, Serda RE, Grattoni A, Bouamrani A, Ferrari M (2010) Emerging applications of nanomedicine for therapy and diagnosis of cardiovascular diseases. Trends Pharmacol Sci 31(5):199–205. doi: 10.1016/ PubMedCentralPubMedCrossRefGoogle Scholar
  33. Gonzalez C, Corbacho AM, Eiserich JP, Garcia C, Lopez-Barrera F, Morales-Tlalpan V, Barajas-Espinosa A, Diaz-Muñoz M, Rubio R, Lin SH, Martinez-de-la-Escalera G, Clapp C (2004) 16 K-prolactin inhibits activation of endothelial nitric oxide synthase, intracellular calcium mobilization, and endothelium-dependent vasorelaxation. Endocrinology 145(12):5714–5722. doi: 10.1210/en.2004-0647 PubMedCrossRefGoogle Scholar
  34. Gonzalez C, Parra A, Ramirez-Peredo J, Garcia C, Rivera JC, Macotela Y, Aranda J, Lemini M, Arias J, Ibargüengoitia F, de-la-Escalera GM, Clapp C (2007) Elevated vasoinhibins may contribute to endothelial cell dysfunction and low birth weight in preeclampsia. Lab Invest 87(10):1009–1017. doi: 10.1038/labinvest.3700662 PubMedCrossRefGoogle Scholar
  35. Gonzalez C, Lemini M, Garcia L, Ramiro-Diaz JM, Castillo-Hernandez JR, Clapp C, Rubio R (2008) Effects of prolactin and vasoinhibins on nitric oxide synthase activity in coronary endothelial cells and vessels in isolated perfused guinea pig hearts. Toxicol Lett 180(1):S34. doi: 10.1016/j.toxlet.2008.06.655 CrossRefGoogle Scholar
  36. Gonzalez C, Salazar-Garcia S, Palestino G, Martinez-Cuevas PP, Ramirez-Lee MA, Jurado-Manzano BB, Rosas-Hernandez H, Gaytan-Pacheco N, Martel G, Espinosa-Tanguma R, Biris AS, Ali SF (2011) Effect of 45 nm silver nanoparticles (AgNPs) upon the smooth muscle of rat trachea: role of nitric oxide. Toxicol Lett 207(3):306–313. doi: 10.1016/j.toxlet.2011.09.024 PubMedCrossRefGoogle Scholar
  37. Grosse S, Evje L, Syversen T (2013) Silver nanoparticle-induced cytotoxicity in rat brain endothelial cell culture. Toxicol In Vitro 27(1):305–313. doi: 10.1016/j.tiv.2012.08.024 PubMedCrossRefGoogle Scholar
  38. Gurunathan S, Lee KJ, Kalishwaralal K, Sheikpranbabu S, Vaidyanathan R, Eom SH (2009) Antiangiogenic properties of silver nanoparticles. Biomaterials 30(31):6341–6350. doi: 10.1016/j.biomaterials.2009.08.008 PubMedCrossRefGoogle Scholar
  39. Gutierrez R, Cubiberti G (2008) Effective models of charge transport in DNA nanowires. In: Shoseyov O, Levy I (eds) NanoBioTechnology bioinspired devices and materials of the future. Human Press Inc., Totowa, pp 108–117Google Scholar
  40. Haase A, Mantion A, Graf P, Plendl J, Thuenemann AF, Meier W, Taubert A, Luch A (2012) A novel type of silver nanoparticles and their advantages in toxicity testing in cell culture systems. Arch Toxicol 86(7):1089–1098. doi: 10.1007/s00204-012-0836-0 PubMedCrossRefGoogle Scholar
  41. Hadrup N, Loeschner K, Bergström A, Wilcks A, Gao X, Vogel U, Frandsen HL, Larsen EH, Lam HR, Mortensen A (2012) Subacute oral toxicity investigation of nanoparticulate and ionic silver in rats. Arch Toxicol 86(4):543–551. doi: 10.1007/s00204-011-0759-1 PubMedCrossRefGoogle Scholar
  42. Hotowy A, Sawosz E, Pineda L, Sawosz F, Grodzik M, Chwalibog A (2012) Silver nanoparticles administered to chicken affect VEGFA and FGF2 gene expression in breast muscle and heart. Nanoscale Res Lett 7(1):418PubMedCentralPubMedCrossRefGoogle Scholar
  43. Hu G, Place AT, Minshall RD (2008) Regulation of endothelial permeability by Src kinase signaling: vascular leakage versus transcellular transport of drugs and macromolecules. Chem Biol Interact 171(2):177–189. doi: 10.1016/j.cbi.2007.08.006 PubMedCentralPubMedCrossRefGoogle Scholar
  44. Jensen LS, Peterson RP, Falen L (1974) Inducement of enlarged hearts and muscular dystrophy in turkey poults with dietary silver. Poult Sci 53:57–64PubMedCrossRefGoogle Scholar
  45. Ji JH, Jung JH, Kim SS, Yoon JU, Park JD, Choi BS, Chung YH, Kwon IH, Jeong J, Han BS, Shin JH, Sung JH, Song KS, Yu IJ (2007) Twenty-eight-day inhalation toxicity study of silver nanoparticles in Sprague–Dawley rats. Inhalation Toxicol 19(10):857–871. doi: 10.1080/08958370701432108 CrossRefGoogle Scholar
  46. Kabanov AV (2006) Polymer genomics: an insight into pharmacology and toxicology of nanomedicines. Adv Drug Deliv Rev 58(15):1597–1621. doi: 10.1016/j.addr.2006.09.019 PubMedCentralPubMedCrossRefGoogle Scholar
  47. Kalishwaralal K, Banumathi E, Ram-Kumar-Pandian S, Deepak V, Muniyandi J, Eom SH, Gurunathan S (2009) Silver nanoparticles inhibit VEGF induced cell proliferation and migration in bovine retinal endothelial cells. Colloids Surf B 73(1):51–57. doi: 10.1016/j.colsurfb.2009.04.025 CrossRefGoogle Scholar
  48. Kang K, Lim DH, Choi IH, Kang T, Lee K, Moon EY, Yang Y, Lee MS, Lim JS (2011) Vascular tube formation and angiogenesis induced by polyvinylpyrrolidone-coated silver nanoparticles. Toxicol Lett 205(3):227–234. doi: 10.1016/j.toxlet.2011.05.1033 PubMedCrossRefGoogle Scholar
  49. Kawabe J, Ushikubi F, Hasebe N (2010) Prostacylcin in vascular diseases, recent insights and future perspectives. Circ J 74(5):836–843. doi: 10.1253/circj.CJ-10-0195 PubMedCrossRefGoogle Scholar
  50. Kennedy DC, Tay LL, Lyn RK, Rouleau Y, Hulse J, Pezacki JP (2009) Nanoscale aggregation of cellular β2-adrenergic receptors measured by plasmonic interactions of functionalized nanoparticles. J Nanosci Nanotechnol 3(8):2329–2339. doi: 10.1021/nn900488u Google Scholar
  51. Kim YS, Kim JS, Cho HS, Rha DS, Kim JM, Park JD, Choi BS, Lim R, Chang HK, Chung YH, Kwon IH, Jeong J, Han BS, Yu IJ (2008) Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague–Dawley rats. Inhal Toxicol 20(6):575–583. doi: 10.1080/08958370701874663 PubMedCrossRefGoogle Scholar
  52. Kim YS, Song MY, Park JD, Song KS, Ryu HR, Chung YH et al (2010) Subchronic oral toxicity of silver nanoparticles. Part Fibre Toxicol 7(20):1–11. doi: 10.1186/1743-8977-7-20 Google Scholar
  53. Klasen HJ (2000) Historical review of the use of silver in the treatment of burns. I. Early uses. Burns 26(2):117–130PubMedCrossRefGoogle Scholar
  54. Korani M, Rezayat SM, Arbabi Bidgoli S (2013) Sub-chronic dermal toxicity of silver nanoparticles in guinea pig: special emphasis to heart, bone and kidney toxicities. Iran J Pharm Res 12(3):511–519PubMedCentralPubMedGoogle Scholar
  55. Krajewski S, Prucek R, Panacek A, Krajewski S, Prucek R, Panacek A, Avci-Adali M, Nolte A, Straub A, Zboril R, Wendel HP, Kvitek L (2013) Hemocompatibility evaluation of different silver nanoparticle concentrations employing a modified Chandler-loop in vitro assay on human blood. Acta Biomater 9(7):7460–7468. doi: 10.1016/j.actbio.2013.03.016 PubMedCrossRefGoogle Scholar
  56. Kumar B, Gupta SK, Saxena R, Srivastava S (2012) Current trends in the pharmacotherapy of diabetic retinopathy. J Postgrad Med 58(2):132–139. doi: 10.4103/0022-3859.97176 PubMedCrossRefGoogle Scholar
  57. Lankveld DPK, Oomen AG, Krystek P, Neigh A, Troost-de-Jong A, Noorlander CW, Van-Eijkeren JC, Geertsma RE, De-Jong WH (2010) The kinetics of the tissue distribution of silver nanoparticles of different sizes. Biomaterials 31(32):8350–8361. doi: 10.1016/j.biomaterials.2010.07.045 PubMedCrossRefGoogle Scholar
  58. Levi D, Tulloch A, Ho J, Kealey C, Rigberg D (2012) Vascular and cardiovascular devices. In: Culjat M, Singh R, Lee H (eds) Medical devices. Surgical and image-guided technologies, 1st edn. Wiley, New York, pp 199–218Google Scholar
  59. Li Z, Carter JD, Dailey LA, Huang YC (2004) Vanadyl sulfate inhibits NO production via threonine phosphorylation of eNOS. Environ Health Perspect 112(2):201–206. doi: 10.1289/ehp.6477 PubMedCentralPubMedCrossRefGoogle Scholar
  60. Li Z, Carter JD, Dailey LA, Huang YC (2005) Pollutant particles produce vasoconstriction and enhance MAPK signaling via angiotensin type I receptor. Environ Health Perspect 113(8):1009–1014. doi: 10.1289/ehp.7736 PubMedCentralPubMedCrossRefGoogle Scholar
  61. Li N, Xia T, Nel AE (2008) The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radical Biol Med 44(9):1689–1699. doi: 10.1016/j.freeradbiomed.2008.01.028 CrossRefGoogle Scholar
  62. Lin Z, Monteiro-Riviere NA, Riviere JE (2014) Pharmacokinetics of metallic nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol. doi: 10.1002/wnan.1304 PubMedCentralGoogle Scholar
  63. Lowry GV, Gregory KB, Apte SC, Lead JR (2012) Transformations of nanomaterials in the environment. Environ Sci Technol 46(13):6893–6899. doi: 10.1021/es300839e PubMedCrossRefGoogle Scholar
  64. Luoma SN (2008) Silver nanotechnologies and the environment: old problems or new challenges? Woodrow Wilson International Center for Scholars, Project on Emerging Nanotechnologies. Pew Charit Trusts 1:66. doi: 10.1093/annhyg/mel071 Google Scholar
  65. Maillard JK, Hartemann P (2013) Silver as an antimicrobial: facts and gaps in knowledge. Crit Rev Microbiol 39(4):373–383. doi: 10.3109/1040841X.2012.713323 PubMedCrossRefGoogle Scholar
  66. Mather KJ, Lteif A, Steinberg HO, Baron AD (2004) Interactions between endothelin and nitric oxide in the regulation of vascular tone in obesity and diabetes. Diabetes 53(8):2060–2066. doi: 10.2337/diabetes.53.8.2060 PubMedCrossRefGoogle Scholar
  67. Moghimi SM, Hunter AC, Murray JC (2001) Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 53(2):283–318PubMedGoogle Scholar
  68. Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Lunts A, Kreyling W, Cox C (2004) Translocation of inhaled ultrafine particles to the brain. Inhalation Toxicol 16(6–7):437–445. doi: 10.1080/00984100290071658 CrossRefGoogle Scholar
  69. Oberdörster G, Oberdörster E, Oberdörster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113(7):823–839. doi: 10.1289/ehp.7339 PubMedCentralPubMedCrossRefGoogle Scholar
  70. Olcott CT (1950) Experimental argyrosis; hypertrophy of the left ventricle of the heart in rats ingesting silver salts. AMA Arch Pathol 49(2):138–149PubMedGoogle Scholar
  71. Pal S, Tak YK, Song JM (2007) Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the gram-negative bacterium Escherichia coli. Appl Environ Microbiol 73(6):1712–1720. doi: 10.1128/AEM.02218-06 PubMedCentralPubMedCrossRefGoogle Scholar
  72. Panyam J, Labhasetwar V (2003) Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 55(3):329–347. doi: 10.1016/S0169-409X(02)00228-4 PubMedCrossRefGoogle Scholar
  73. Peters K, Unger RE, Kirkpatrick CJ, Gatti AM, Monari E (2004) Effects of nano-scaled particles on endothelial cell function in vitro: studies on viability, proliferation and inflammation. J Mater Sci - Mater Med 15(4):321–325. doi: 10.1023/B:JMSM.0000021095.36878.1b PubMedCrossRefGoogle Scholar
  74. Peterson RP, Jensen LS, Harrison PC (1973) Effect of silver-induced enlarged hearts during the first four weeks of life on subsequent performance of turkeys. Avian Dis 17:802–806PubMedCrossRefGoogle Scholar
  75. Polverini PJ (2002) Angiogenesis in health and disease: insights into basic mechanisms and therapeutic opportunities. J Dent Educ 66(8):962–975PubMedGoogle Scholar
  76. Quadros ME, Marr LC (2010) Environmental and human health risks of aerosolized silver nanoparticles. J Air Waste Manag Assoc 60(7):770–781. doi: 10.3155/1047-3289.60.7.770 PubMedCrossRefGoogle Scholar
  77. Rahman MF, Wang J, Patterson TA, Saini UT, Robinson BL, Newport GD, Murdock RC, Schlager JJ, Hussain SM, Ali SF (2009) Expression of genes related to oxidative stress in the mouse brain after exposure to silver-25 nanoparticles. Toxicol Lett 187(1):15–21. doi: 10.1016/j.toxlet.2009.01.020 PubMedCrossRefGoogle Scholar
  78. Red-Horse K, Ueno H, Weissman IL, Krasnow MA (2010) Coronary arteries form by developmental reprogramming of venous cells. Nature 464(7288):549–553. doi: 10.1038/nature08873 PubMedCentralPubMedCrossRefGoogle Scholar
  79. Ricciardolo FL, Maria DGU, Mistretta A (1997) Impairment of bronchoprotection by nitric oxide in severe asthma. The Lancet 350(9087):1297–1298. doi: 10.1016/S0140-6736(05)62474-9 CrossRefGoogle Scholar
  80. Rosas-Hernandez H, Jimenez-Badillo S, Martinez-Cuevas PP, Gracia-Espino E, Terrones H, Terrones M, Hussain SM, Ali SF, Gonzalez C (2009) Effects of 45-nm silver nanoparticles on coronary endothelial cells and isolated rat aortic rings. Toxicol Lett 191(2–3):305–313. doi: 10.1016/j.toxlet.2009.09.014 PubMedCrossRefGoogle Scholar
  81. Salata O (2004) Applications of nanoparticles in biology and medicine. J Nanobiotechnol 2(1):3. doi: 10.1186/1477-3155-2-3 CrossRefGoogle Scholar
  82. Sarhan OM, Hussein RM (2014) Effects of intraperitoneally injected silver nanoparticles on histological structures and blood parameters in the albino rat. Int J Nanomed 24(9):1505–1517. doi: 10.2147/IJN.S56729 Google Scholar
  83. Schrand AM, Rahman MF, Hussain SM, Schlager JJ, Smith DA, Syed AF (2010) Metal-based nanoparticles and their toxicity assessment. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2(5):544–568. doi: 10.1002/wnan.103 PubMedCrossRefGoogle Scholar
  84. Sharma HS, Ali SF, Hussain SM, Schlager JJ, Sharma A (2009a) Influence of engineered nanoparticles from metals on the blood–brain barrier permeability, cerebral blood flow, brain edema and neurotoxicity. An experimental study in the rat and mice using biochemical and morphological approaches. J Nanosci Nanotechnol 9(8):5055–5072. doi: 10.1166/jnn.2009.GR09 PubMedCrossRefGoogle Scholar
  85. Sharma HS, Ali SF, Tian ZR, Hussain SM, Schlager JJ, Sjöquist PO, Sharma A, Muresanu DF (2009b) Chronic treatment with nanoparticles exacerbate hyperthermia induced blood–brain barrier breakdown, cognitive dysfunction and brain pathology in the rat. Neuroprotective effects of nanowired-antioxidant compound H-290/51. J Nanosci Nanotechnol 9(8):5073–5090. doi: 10.1166/jnn.2009.GR10 PubMedCrossRefGoogle Scholar
  86. Sheikpranbabu S, Kalishwaralal K, Venkataraman D, Eom SH, Park J, Gurunathan S (2009) Silver nanoparticles inhibit VEGF-and IL-1beta—induced vascular permeability via Src dependent pathway in porcine retinal endothelial cells. J Nanobiotechnol 7:8. doi: 10.1186/1477-3155-7-8 CrossRefGoogle Scholar
  87. Sheikpranbabu S, Kalishwaralal K, Lee K, Vaidyanathan R, Eom SH, Gurunathan S (2010) The inhibition of advanced glycation end-products-induced retinal vascular permeability by silver nanoparticles. Biomaterials 31(8):2260–2271. doi: 10.1016/j.biomaterials.2009.11.076 PubMedCrossRefGoogle Scholar
  88. Shi J, Sun X, Lin Y, Zou X, Li Z, Liao Y, Du M, Zhang H (2014) Endothelial cell injury and dysfunction induced by silver nanoparticles through oxidative stress via IKK/NF-κB pathways. Biomaterials 35(24):6657–6666. doi: 10.1016/j.biomaterials.2014.04.093 PubMedCrossRefGoogle Scholar
  89. Soto K, Garza KM, Murr LE (2007) Cytotoxic effects of aggregated nanomaterials. Acta Biomater 3(3):351–358. doi: 10.1016/j.actbio.2006.11.004 PubMedCrossRefGoogle Scholar
  90. Sriram M, Kanth S, Kalishwaralal K, Gurunathan S (2010) Antitumor activity of silver nanoparticles in Dalton’s lymphoma ascites tumor model. Int J Nanomed 5:753–762. doi: 10.2147/IJN.S11727 Google Scholar
  91. Sung J, Ji JH, Yoon J, Kim DS, Song MY, Jeong J, Han BS, Han JH, Chung YH, Kim J, Kim TS, Chang HK, Lee EJ, Lee JH, Yu IJ (2008) Lung function changes in Sprague–Dawley rats after prolonged inhalation exposure to silver nanoparticles. Inhalation Toxicol 20(6):567–574. doi: 10.1080/08958370701874671 CrossRefGoogle Scholar
  92. Sung J, Ji J, Park JD, Yoon JU, Kim DS, Jeon KS, Song MY, Jeong J, Han BS, Han JH, Chung YH, Chang HK, Lee JH, Cho MH, Kelman BJ, Yu IJ (2009) Subchronic inhalation toxicity of silver nanoparticles. Toxicol Sci 108(2):452–461. doi: 10.1093/toxsci/kfn246 PubMedCrossRefGoogle Scholar
  93. Takenaka S, Karg E, Roth C, Schulz H, Ziesenis A, Heinzmann U, Schramel P, Heyder J (2001) Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ Health Perspect 109(4):547–551. doi: 10.1007/s00204-010-0545-5 PubMedCentralPubMedCrossRefGoogle Scholar
  94. Tang J, Xiong L, Wang S, Wang J, Liu L, Li J, Yuan F, Xi T (2009) Distribution, translocation and accumulation of silver nanoparticles in rats. J Nanosci Nanotechnol 9(8):4924–4932. doi: 10.1166/jnn.2009.1269 PubMedCrossRefGoogle Scholar
  95. Tang J, Xiong L, Zhou G, Wang S, Wang J, Liu L, Li J, Yuan F, Lu S, Wan Z, Chou L, Xi T (2010) silver nanoparticles crossing through and distribution in the blood–brain barrier in vitro. J Nanosci Nanotechnol 10(10):6313–6317. doi: 10.1166/jnn.2010.2625 PubMedCrossRefGoogle Scholar
  96. Thum T, Bauersachs J (2006) Growth hormone regulates vascular function what we know from bench and bedside. Eur J Clin Pharmacol 62(1):29–32. doi: 10.1007/s00228-005-0018-6 CrossRefGoogle Scholar
  97. Tirapelli CR, Bonaventura D, Tirapelli LF, de-Oliveira AM (2009) Mechanisms underlying the vascular actions of endothelin 1, angiotensin II and bradykinin in the rat carotid. Pharmacology 84(2):111–126. doi: 10.1159/000231974 PubMedCrossRefGoogle Scholar
  98. Trickler WJ, Lantz SM, Murdock RC, Schrand AM, Robinson BL, Newport GD, Schlager JJ, Oldenburg SJ, Paule MG, Slikker W Jr, Hussain SM, Ali SF (2010) Silver nanoparticle induced blood–brain barrier inflammation and increased permeability in primary rat brain microvessel endothelial cells. Toxicol Sci 118(1):160–170. doi: 10.1093/toxsci/kfq244 PubMedCrossRefGoogle Scholar
  99. Tsai B, Wang M, Turrentine M, Mahomed Y, Brown JW, Meldrum DR (2004) Hypoxic pulmonary vasoconstriction in cardiothoracic surgery: basic mechanisms to potential therapies. Ann Thorac Surg 78(1):360–368. doi: 10.1016/j.athoracsur.2003.11.035 PubMedCrossRefGoogle Scholar
  100. Venema VJ, Marrero MB, Venema RC (1996) Bradykinin-stimulated protein tyrosine phosphorylation promotes endothelial nitric oxide synthase translocation to the cytoskeleton. Biochem Biophys Res Commun 226(3):703–710. doi: 10.1006/bbrc.1996.1417 PubMedCrossRefGoogle Scholar
  101. Westfall TC, Westfall DP (2011) Adrenergic agonists and antagonists. In: Brunton L (ed) Goodman and Gilman’s: the pharmacological basis of therapeutics, 12th edn. McGraw-Hill, New York, pp 277–333Google Scholar
  102. Xu Y, Tang H, Liu JH, Wang H, Liu Y (2013) Evaluation of the adjuvant effect of silver nanoparticles both in vitro and in vivo. Toxicol Lett 219(1):42–48. doi: 10.1016/j.toxlet.2013.02.010 PubMedCrossRefGoogle Scholar
  103. Zamudio A, Elias A, Rodriguez-Manzo JA, Lopez-Urias F, Rodriguez-Gattorno G, Lupo F, Rühle M, Smith DJ, Terrones H, Diaz D, Terrones M (2006) Efficient anchoring of silver nanoparticles on N-doped carbon nanotubes. Small 2(3):346–350. doi: 10.1002/smll.200500348 PubMedCrossRefGoogle Scholar
  104. Zhang W, Zhang Q, Wang F, Yuan L, Jiang F, Liu Y (2014) Comparison of interactions between human serum albumin and silver nanoparticles of different sizes using spectroscopic methods. Luminescence. doi: 10.1002/bio.2748 Google Scholar
  105. Zheng Y, He M, Congdon N (2012) The worldwide epidemic of diabetic retinopathy. Indian J Ophthalmol 60(5):428–431. doi: 10.4103/0301-4738.100542 PubMedCentralPubMedCrossRefGoogle Scholar
  106. Zlokovic BV (2008) The blood–brain barrier in health and chronic neurodegenerative disorders. Neuron 57(2):178–201. doi: 10.1016/j.neuron.2008.01.003 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Carmen Gonzalez
    • 1
    • 2
    Email author
  • Hector Rosas-Hernandez
    • 1
  • Manuel Alejandro Ramirez-Lee
    • 1
  • Samuel Salazar-García
    • 1
  • Syed F. Ali
    • 2
  1. 1.Facultad de Ciencias QuimicasUniversidad Autonoma de San Luis PotosiSan Luis PotosiMexico
  2. 2.Neurochemistry Laboratory, Division of NeurotoxicologyNational Center for Toxicological ResearchJeffersonUSA

Personalised recommendations