Silencing Human VCAM 1 Gene
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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 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.
- 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):1553–1557CrossRefPubMedGoogle 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):60–65CrossRefPubMedGoogle 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):2266–2271PubMedGoogle 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):5257–5267PubMedGoogle 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):497–512CrossRefPubMedPubMedCentralGoogle 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):368–374CrossRefGoogle 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):237–251CrossRefPubMedPubMedCentralGoogle 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):347–355CrossRefPubMedPubMedCentralGoogle Scholar