Skip to main content

Silencing Human VCAM 1 Gene

  • Chapter
  • First Online:
Advances in Animal Biotechnology and its Applications
  • 1091 Accesses

Abstract

One of the key steps in the initiation of atherosclerosis is the adhesion of leukocytes on the activated vascular endothelial cells and their relocation into the vessel wall. This occurs because of the upregulation of the adhesion/attachment particles like vascular cell adhesion molecule-1 (VCAM-1) on the activated vascular endothelial cells and an expanded expression in the vascular mass of chemotactic elements to the monocytes. Similar mechanisms in reverse underlie cancer cell metastasis and other inflammatory disease processes. So interfering with VCAM1 expression could be a valuable approach to prevention and cure of diseases as diverse as atherosclerosis, cancer, graft rejection, etc. The beginnings of RNA interference (RNAi) as a gene knockdown technique symbolize an electrifying improvement in the field of small-molecule nucleic acid-based therapeutics. Present review is focused on the gene VCAM1, as a target for development of potential new therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alam AK, Florey O, Weber M, Pillai RG, Chan C, Tan PH, Lechler RI, McClure MO, Haskard DO, George AJ (2006) Knockdown of mouse VCAM-1 by vector-based siRNA. Transpl Immunol 16(3–4):185–193

    Article  CAS  PubMed  Google Scholar 

  • Allen E, Xie Z, Gustafson AM, Carrington JC (2005) microRNA-directed phasing during trans-acting siRNA biogenesis in plants. Cell 121(2):207–221

    Article  CAS  Google Scholar 

  • Aomatsu E, Chosa N, Nishihira S, Sugiyama Y, Miura H, Ishisaki A (2014) Cell-cell adhesion through N-cadherin enhances VCAM-1 expression via PDGFR beta in a ligand-independent manner in mesenchymal stem cells. Int J Mol Med 33(3):565–572

    Article  CAS  PubMed  Google Scholar 

  • Barthel SR, Annis DS, Mosher DF, Johansson MW (2006) Differential engagement of modules 1 and 4 of vascular cell adhesion molecule-1 (CD106) by integrins alpha4beta1 (CD49d/29) and alphaMbeta2 (CD11b/18) of eosinophils. J Biol Chem 281(43):32175–32187

    Article  CAS  PubMed  Google Scholar 

  • Besemer J, Harant H, Wang S, Oberhauser B, Marquardt K, Foster CA, Schreiner EP, de Vries JE, Dascher-Nadel C, Lindley IJ (2005) Selective inhibition of cotranslational translocation of vascular cell adhesion molecule 1. Nature 436(7048):290–293

    Article  CAS  Google Scholar 

  • Bochner BS, Luscinskas FW, Gimbrone MA Jr, Newman W, Sterbinsky SA, Derse-Anthony CP, Klunk D, Schleimer RP (1991) Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules. J Exp Med 173(6):1553–1557

    Article  CAS  PubMed  Google Scholar 

  • Bumcrot D, Manoharan M, Koteliansky V, Sah DW (2006) RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol 2(12):711–719

    Article  CAS  PubMed  Google Scholar 

  • Campbell DJ, Woodward M, Chalmers JP, Colman SA, Jenkins AJ, Kemp BE, Neal BC, Patel A, MacMahon SW (2006) Soluble vascular cell adhesion molecule 1 and N-terminal pro-B-type natriuretic peptide in predicting ischemic stroke in patients with cerebrovascular disease. Arch Neurol 63(1):60–65

    Article  PubMed  Google Scholar 

  • Carlos T, Kovach N, Schwartz B, Rosa M, Newman B, Wayner E, Benjamin C, Osborn L, Lobb R, Harlan J (1991) Human monocytes bind to two cytokine-induced adhesive ligands on cultured human endothelial cells: endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1. Blood 77(10):2266–2271

    PubMed  CAS  Google Scholar 

  • Chiu HH, Crowe DT, Renz ME, Presta LG, Jones S, Weissman IL, Fong S (1995) Similar but nonidentical amino acid residues on vascular cell adhesion molecule-1 are involved in the interaction with alpha 4 beta 1 and alpha 4 beta 7 under different activity states. J Immunol 155(11):5257–5267

    PubMed  CAS  Google Scholar 

  • Cook-Mills JM (2002) VCAM-1 signals during lymphocyte migration: role of reactive oxygen species. Mol Immunol 39(9):499–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Costa MF, Bornstein VU, Candea AL, Henriques-Pons A, Henriques MG, Penido C (2012) CCL25 induces alpha(4)beta(7) integrin-dependent migration of IL-17(+) gamma delta T lymphocytes during an allergic reaction. Eur J Immunol 42(5):1250–1260

    Article  CAS  PubMed  Google Scholar 

  • Cybulsky MI, Fries JW, Williams AJ, Sultan P, Eddy R, Byers M, Shows T, Gimbrone MA Jr, Collins T (1991) Gene structure, chromosomal location, and basis for alternative mRNA splicing of the human VCAM1 gene. Proc Natl Acad Sci U S A 88(17):7859–7863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dutta P, Hoyer FF, Grigoryeva LS, Sager HB, Leuschner F, Courties G, Borodovsky A, Novobrantseva T, Ruda VM, Fitzgerald K, Iwamoto Y, Wojtkiewicz G, Sun Y, Da Silva N, Libby P, Anderson DG, Swirski FK, Weissleder R, Nahrendorf M (2015) Macrophages retain hematopoietic stem cells in the spleen via VCAM-1. J Exp Med 212(4):497–512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411(6836):494–498

    Article  CAS  PubMed  Google Scholar 

  • Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669):806–811

    Article  CAS  Google Scholar 

  • Freedman AS, Munro JM, Rice GE, Bevilacqua MP, Morimoto C, McIntyre BW, Rhynhart K, Pober JS, Nadler LM (1990) Adhesion of human B cells to germinal centers in vitro involves VLA-4 and INCAM-110. Science 249(4972):1030–1033

    Article  CAS  PubMed  Google Scholar 

  • Funk PE, Kincade PW, Witte PL (1994) Native associations of early hematopoietic stem cells and stromal cells isolated in bone marrow cell aggregates. Blood 83(2):361–369

    PubMed  CAS  Google Scholar 

  • Garcia-Bernal D, Sotillo-Mallo E, Nombela-Arrieta C, Samaniego R, Fukui Y, Stein JV, Teixido J (2006) DOCK2 is required for chemokine-promoted human T lymphocyte adhesion under shear stress mediated by the integrin alpha4beta1. J Immunol 177(8):5215–5225

    Article  CAS  PubMed  Google Scholar 

  • Garmy-Susini B, Jin H, Zhu Y, Sung RJ, Hwang R, Varner J (2005) Integrin alpha4beta1-VCAM-1-mediated adhesion between endothelial and mural cells is required for blood vessel maturation. J Clin Invest 115(6):1542–1551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Golden DE, Gerbasi VR, Sontheimer EJ (2008) An inside job for siRNAs. Mol Cell 31(3):309–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ (2008) MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A 105(5):1516–1521

    Article  PubMed  PubMed Central  Google Scholar 

  • Hession C, Tizard R, Vassallo C, Schiffer SB, Goff D, Moy P, Chi-Rosso G, Luhowskyj S, Lobb R, Osborn L (1991) Cloning of an alternate form of vascular cell adhesion molecule-1 (VCAM1). J Biol Chem 266(11):6682–6685

    PubMed  CAS  Google Scholar 

  • Huang J, Zhang J, Li H, Lu Z, Shan W, Mercado-Uribe I, Liu J (2013) VCAM1 expression correlated with tumorigenesis and poor prognosis in high grade serous ovarian cancer. Am J Transl Res 5(3):336–346

    PubMed  PubMed Central  CAS  Google Scholar 

  • Khachigian LM, Collins T, Fries JW (1995) Nuclear factor-kappa B mediates induction of vascular cell adhesion molecule-1 in glomerular mesangial cells. Biochem Biophys Res Commun 206(2):462–467

    Article  CAS  PubMed  Google Scholar 

  • Kilger G, Needham LA, Nielsen PJ, Clements J, Vestweber D, Holzmann B (1995) Differential regulation of alpha 4 integrin-dependent binding to domains 1 and 4 of vascular cell adhesion molecule-1. J Biol Chem 270(11):5979–5984

    Article  CAS  PubMed  Google Scholar 

  • Klemke M, Weschenfelder T, Konstandin MH, Samstag Y (2007) High affinity interaction of integrin alpha4beta1 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) enhances migration of human melanoma cells across activated endothelial cell layers. J Cell Physiol 212(2):368–374

    Article  CAS  Google Scholar 

  • Kon S, Atakilit A, Sheppard D (2011) Short form of alpha9 promotes alpha9beta1 integrin-dependent cell adhesion by modulating the function of the full-length alpha9 subunit. Exp Cell Res 317(12):1774–1784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kowalski PS, Lintermans LL, Morselt HW, Leus NG, Ruiters MH, Molema G, Kamps JA (2013) Anti-VCAM-1 and anti-E-selectin SAINT-O-Somes for selective delivery of siRNA into inflammation-activated primary endothelial cells. Mol Pharm 10(8):3033–3044

    Article  CAS  PubMed  Google Scholar 

  • Lee IT, Shih RH, Lin CC, Chen JT, Yang CM (2012) Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells. Cell Commun Signal 10(1):33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lessner SM, Prado HL, Waller EK, Galis ZS (2002) Atherosclerotic lesions grow through recruitment and proliferation of circulating monocytes in a murine model. Am J Pathol 160(6):2145–2155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lippman Z, Martienssen R (2004) The role of RNA interference in heterochromatic silencing. Nature 431(7006):364–370

    Article  CAS  Google Scholar 

  • Lu TT, Cyster JG (2002) Integrin-mediated long-term B cell retention in the splenic marginal zone. Science 297(5580):409–412

    Article  CAS  PubMed  Google Scholar 

  • Manka DR, Wiegman P, Din S, Sanders JM, Green SA, Gimple LW, Ragosta M, Powers ER, Ley K, Sarembock IJ (1999) Arterial injury increases expression of inflammatory adhesion molecules in the carotid arteries of apolipoprotein-E-deficient mice. J Vasc Res 36(5):372–378

    Article  CAS  PubMed  Google Scholar 

  • Mello CC, Conte D Jr (2004) Revealing the world of RNA interference. Nature 431(7006):338–342

    Article  CAS  Google Scholar 

  • Neish AS, Williams AJ, Palmer HJ, Whitley MZ, Collins T (1992) Functional analysis of the human vascular cell adhesion molecule 1 promoter. J Exp Med 176(6):1583–1593

    Article  CAS  PubMed  Google Scholar 

  • Olson EN, Srivastava D (1996) Molecular pathways controlling heart development. Science 272(5262):671–676

    Article  CAS  PubMed  Google Scholar 

  • Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G, Lobb R (1989) Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell 59(6):1203–1211

    Article  CAS  PubMed  Google Scholar 

  • Pan F, Yang T-L, Chen X-D, Chen Y, Gao G, Liu Y-Z, Pei Y-F, Sha B-Y, Jiang Y, Xu C, Recker RR, Deng H-W (2010) Impact of female cigarette smoking on circulating B cells in vivo: the suppressed ICOSLG, TCF3, and VCAM1 gene functional network may inhibit normal cell function. Immunogenetics 62(4):237–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petersen EJ, Miyoshi T, Yuan Z, Hirohata S, Li JZ, Shi W, Angle JF (2008) siRNA silencing reveals role of vascular cell adhesion molecule-1 in vascular smooth muscle cell migration. Atherosclerosis 198(2):301–306

    Article  CAS  PubMed  Google Scholar 

  • Qu Y, Shi X, Zhang H, Sun W, Han S, Yu C, Li J (2009) VCAM-1 siRNA reduces neointimal formation after surgical mechanical injury of the rat carotid artery. J Vasc Surg 50(6):1452–1458

    Article  PubMed  Google Scholar 

  • Radecke CE, Warrick AE, Singh GD, Rogers JH, Simon SI, Armstrong EJ (2015) Coronary artery endothelial cells and microparticles increase expression of VCAM-1 in myocardial infarction. Thromb Haemost 113(3):605–616

    Article  PubMed  Google Scholar 

  • Rice GE, Bevilacqua MP (1989) An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science 246(4935):1303–1306

    Article  CAS  PubMed  Google Scholar 

  • Rice GE, Munro JM, Corless C, Bevilacqua MP (1991) Vascular and nonvascular expression of INCAM-110. A target for mononuclear leukocyte adhesion in normal and inflamed human tissues. Am J Pathol 138(2):385–393

    PubMed  PubMed Central  CAS  Google Scholar 

  • Ruegg C, Postigo AA, Sikorski EE, Butcher EC, Pytela R, Erle DJ (1992) Role of integrin alpha 4 beta 7/alpha 4 beta P in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering. J Cell Biol 117(1):179–189

    Article  CAS  PubMed  Google Scholar 

  • Shin J, Kim J, Ryu B, Chi SG, Park H (2006) Caveolin-1 is associated with VCAM-1 dependent adhesion of gastric cancer cells to endothelial cells. Cell Physiol Biochem 17(5–6):211–220

    Article  CAS  PubMed  Google Scholar 

  • Simionescu M, Simionescu N (1993) Proatherosclerotic events: pathobiochemical changes occurring in the arterial wall before monocyte migration. FASEB J 7(14):1359–1366

    Article  CAS  PubMed  Google Scholar 

  • Singh RJ, Mason JC, Lidington EA, Edwards DR, Nuttall RK, Khokha R, Knauper V, Murphy G, Gavrilovic J (2005) Cytokine stimulated vascular cell adhesion molecule-1 (VCAM-1) ectodomain release is regulated by TIMP-3. Cardiovasc Res 67(1):39–49

    Article  CAS  PubMed  Google Scholar 

  • Slack-Davis JK, Atkins KA, Harrer C, Hershey ED, Conaway M (2009) Vascular cell adhesion molecule-1 is a regulator of ovarian cancer peritoneal metastasis. Cancer Res 69(4):1469–1476

    Article  CAS  PubMed  Google Scholar 

  • Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76(2):301–314

    Article  CAS  Google Scholar 

  • Springer TA (1995) Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol 57:827–872

    Article  CAS  PubMed  Google Scholar 

  • Sun H-J, Zhao M-X, Liu T-Y, Ren X-S, Chen Q, Li Y-H, Kang Y-M, Zhu G-Q (2016) Salusin-β induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NFκB pathway. Sci Rep 6:23596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taichman DB, Cybulsky MI, Djaffar I, Longenecker BM, Teixido J, Rice GE, Aruffo A, Bevilacqua MP (1991) Tumor cell surface alpha 4 beta 1 integrin mediates adhesion to vascular endothelium: demonstration of an interaction with the N-terminal domains of INCAM-110/VCAM-1. Cell Regul 2(5):347–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vazquez F, Vaucheret H, Rajagopalan R, Lepers C, Gasciolli V, Mallory AC, Hilbert JL, Bartel DP, Crete P (2004) Endogenous trans-acting siRNAs regulate the accumulation of Arabidopsis mRNAs. Mol Cell 16(1):69–79

    Article  CAS  PubMed  Google Scholar 

  • Walker T, Wendel HP, Tetzloff L, Raabe C, Heidenreich O, Simon P, Scheule AM, Ziemer G (2007) Inhibition of adhesion molecule expression on human venous endothelial cells by non-viral siRNA transfection. J Cell Mol Med 11(1):139–147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walker T, Siegel J, Nolte A, Hartmann S, Kornberger A, Steger V, Wendel HP (2011) Small interfering RNA efficiently suppresses adhesion molecule expression on pulmonary microvascular endothelium. J Nucleic Acids 2011:694789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walsh GM, Symon FA, Lazarovils AL, Wardlaw AJ (1996) Integrin alpha 4 beta 7 mediates human eosinophil interaction with MAdCAM-1, VCAM-1 and fibronectin. Immunology 89(1):112–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang PC, Weng CC, Hou YS, Jian SF, Fang KT, Hou MF, Cheng KH (2014) Activation of VCAM-1 and its associated molecule CD44 leads to increased malignant potential of breast cancer cells. Int J Mol Sci 15(3):3560–3579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgement

This work was supported by Department of Biotechnology, New Delhi [Project No. BT/PR10694/AGR/36/587/2008], University Grants Commission, New Delhi [F.14-2(SC)/2009 (SA-III)] and the grant from DBT Interdisciplinary Life Sciences Programme for Advance Research and Education [DBT-IPLS Project No BT/PR4548/INF/22/146/2012]; Punjabi University, Patiala.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kapoor, D., Balgir, P.P. (2018). Silencing Human VCAM 1 Gene. In: Gahlawat, S., Duhan, J., Salar, R., Siwach, P., Kumar, S., Kaur, P. (eds) Advances in Animal Biotechnology and its Applications. Springer, Singapore. https://doi.org/10.1007/978-981-10-4702-2_3

Download citation

Publish with us

Policies and ethics