Scientists are working on developing a tagged antibody, which will identify atherosclerotic plaque and fat in the walls of arteries. Deposits are threatening with wall rupture and thrombus, so as a consequence with heart attack or ischemic brain stroke. The results of studies on the antibody were published in Circulation Research, journal of the American Heart Association (AHA).
Heart attack and ischemic brain stroke occur most commonly on the background of atherosclerotic changes as a result of the instability of the plaque. Atherosclerosis is a common example of the inflammation process, which dynamics – and not only the same presence – remains in correlation with clinical signs. The exponent of atherosclerosis is artery walls bolding (inner and muscle layer – intima/media). In the early stages of atherogenesis it comes to infiltration of the vessel walls with monocytes. Adhesion molecules are present on the surface of leucocytes and endothelial cells, and they are receptors of interaction with other cells and mediators of leucocytes migration outside blood vessels to the core of immunological reaction. Although the name of molecules refers to the adhesion, its initialization is only one of many of their functions. Process of leucocytes penetration is affected by numerous cytokines, chemoattractants and adhesion molecules, such as ICAM-1 and VCAM-1. In places where monocytes penetrate, the damage to the endothelial cells and deposits of intercellular matrix (matrix-retains), and often also the presence of modified lipoproteins can be observed. The accumulation of oxidised LDL lipoproteins in vessels inner layer is the factor triggering the cascade of inflammatory reaction. Molecules VCAM-1 (encoded by the VCAM1 gene located on chromosome 1 locus 1p31-32) are present on the endothelial cells and antigen presenting cells. Lymphocytes, granulocytes and macrophages membrane receptor for VCAM-1 is adhesive molecule VLA-4. Thanks to the interaction of these proteins, T cells response is initiated, which is very important in the early development of inflammation process. In studies of patients with acute coronary syndrome the role of VCAM-1 as a predicting factor of higher cardiovascular incident risk was suggested. The association of VCAM-1 concentrations with severity of inflammation process assessed on the basis of measurement of the concentration of C-reactive protein was observed.
A team of scientists from the University of Grenoble in France and Harvard Medical School in Boston – USA, is working on developing a radioactive tagged antibody, which binds with the atherosclerotic plaque in vessels. The study is significant, because until today we have no noninvasive method to assess the state of the arteries, especially the coronary. Diagnosis of deposits in vessels enables the treatment before heart attack or ischemic brain stroke occurrence. The scientists created nanoantibody, which binds with the adhesion molecule VCAM-1, localized normally on endothelial cells, but also within the atherosclerotic plaque. Inflammation present in the plaque increases the expression of VCAM-1, and thus the molecules density in the place affected by lesions. Using the animal model – mice were given solution containing marked antibodies, and then a single-proton emission computed tomography (SPECT/CT) was performed. It was found that the nanoantibodies bound with the VCAM-1 and remained in mice living organisms for 6 hours. It appeared that atherosclerotic plaques located in the tested animals aortas were especially dense. If scientists will receive the appropriate permission, these studies will be repeated in humans. An important issue is the assessment whether the antibodies that bind with VCAM-1 does not change their natural function. Observations are continued. Will the antibodies conquer the atherosclerosis?
1. A. Broisat, S. Hernot, J. Toczek, J. De Vos, L. M. Riou, S. Martin, M. Ahmadi, N. Thielens, U. Wernery, V. Caveliers, S. Muyldermans, T. Lahoutte, D. Fagret, C. Ghezzi, N. Devoogdt. Nanobodies Targeting Mouse/Human VCAM1 for the Nuclear Imaging of Atherosclerotic Lesions. Circulation Research, 2012; 110 (7): 927 DOI: 10.1161/CIRCRESAHA.112.265140
2. Radioactive antibody fragment may help scientists identify artery deposits. ScienceDaily. Retrieved July 25, 2012, from http://www.sciencedaily.com /releases/2012/03/120329170429.htm
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