FP6Индивидуална стипендия2007–2010

MOLECULAR IMAGING · Molecular imaging of Atherosclerosis

6РП — Действия „Мария Кюри“

Период: 2007-01-08 → 2010-01-07
Финансиране от ЕС: 246 464 €
Участници: 2
Схема: OIF

Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.

Накратко на български

Ензимът миелопероксидаза се проучва като маркер за откриване на болестта Алцхаймер чрез нови контрастни вещества за ЯМР. Това помага за по-точното идентифициране на ранните етапи на заболяването и свързания с него окислителен стрес в мозъка.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Final Activity and Management Report Summary - MOLECULAR IMAGING (Molecular Imaging of Atherosclerosis)

Myeloperoxidase (MPO) is a key component of the antimicrobial armoury of neutrophils. In the presence of hydrogen peroxide, MPO can generate a variety of reactive oxygen species against microorganisms. Besides its role in host defence, MPO has been implicated in the pathophysiology of cardiovascular and neurodegenerative diseases, likely by causing an increase in oxidative stress. During the first part of the project, three new compounds were synthesised and well-characterised as substrates for MPO detection. These compounds were based on the conjugation of aromatic amines which can interact with the MPO, to the chelating agent, DTPA, which allows these compounds to complex with the gadolinium ion, making these compounds into imaging agents for Magnetic Resonance Imaging (MRI). The ability of our compounds to interact with myeloperoxidase depends on the redox potential values of the resultant imaging agents and the interaction of the complexes with the MPO results in radical generation. Indeed, it has been reported that an increase of MPO expression and related oxidative products were found in neurons in human patients with Alzheimer's disease (AD). Therefore, we aimed to identify if the myeloperoxidase enzyme would be a good biomarker to detect AD. We identified intracellular MPO in 3xTg-AD mice at the early phases of the disease (6-7 months) by immunohistochemistry techniques. The labelling was stronger in older animals. MPO was mainly detected in the pyramidal neurons of hippocampus and amygdala, which are also the preferential sites of intraneuronal amyloid-? deposits in this AD animal model. Confirming last result, RT-PCR showed an increase in the MPO expression in transgenic mice versus control mice. In vitro MPO characterisation using the neuronal cell line, MC65, which mimics the accumulation of the amyloid-? in neurons by expression of a partial APP fusion protein, was carried out. An increase in the MPO activity and in the expression was observed due to the accumulation of amyloidogenic peptides, confirming the active paper of the MPO in AD. Finally, since AD presents from the beginning of the disease a chronic inflammatory response, we created an inflammatory scenario using a mix of cytokines: Il-1? and IFN-? and we treated the human neuronal cell line SK-NMC with them. After treatment, MPO activity had increased, confirming the inflammatory role of the MPO in neurons at the very early stage of the disease. All these results suggest that our MRI imaging probes that target MPO could be used to detect AD prior to the development of amyloid-? deposits.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The leading cause of morbidity and mortality in developed nations is vascular disease such as cardiovascular disease and cerebrovascular disease. The process common to these diseases is atherosclerosis, and in particular, the formation of vulnerable plaques those rupture and cause thromboembolic disease1.Therefore, there exists a need to develop a non-invasive strategy that can detect and assess vulnerable plaques prior to plaque rupture that can provide both high-resolution anatomic and functional information with a high degree of sensitivity and specificity. Myeloperoxidase (MPO) has been identified as a marker of active inflammation in vulnerable plaques.Elevated plasma MPO concentrations have been found in stroke and myocardial infarction2. Thus, MPO i s evolving as a key molecular and clinical biomarker of vulnerable plaques. The Weissleder group has recently developed a novel approach for imaging peroxidases using low molecular weight paramagnetic enzyme substrates3.The overall goal of this proposal i s to develop and test novel activatable molecular imaging agents that can sense MPO activity in vivo, and to expose the candidate to state of the art molecular imaging techniques in an integrated multidisciplinary environment.These smart" agents harness enzyme-mediated amplification and are potentially much more sensitive than alternative targeted agents. We hypothesize that MPO substrates are converted into highly reactive self-polymerizing intermediates that give oligomers with high relaxivity.Preliminary data have shown that these novel agents can be used to report enzyme activity by MRI and nuclear medicine. 1. Libby P. Nature 2002;420(6917):868-874. 2. Brennan ML et al. N Engl J Med 2003;349(17):1595-1604. 3. Chen JW et al. Magn Reson Med 2004"

Оригинален текст от CORDIS (на английски).

Участници

SPANISH COUNCIL FOR SCIENTIFIC RESEARCH · MADRIDКоординаторНиво градИспания
CENTER FOR MOLECULAR IMAGING RESEARCH · CHARLESTOWN, MAНиво държаваСъединени щати