H2020Индивидуална стипендия2016–2019

MERC · Molecular mechanisms regulating cardiovascular remodeling by Adamts1

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2016-06-01 → 2019-11-15
Финансиране от ЕС: 170 122 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Молекулярните механизми на гена Adamts1 се изследват чрез мишки, за да се разбере как се развиват аневризмите на възходящата аорта. Познаването на тези процеси помага за разработването на лекарствени стратегии, които да подобрят качеството и продължителността на живот на пациентите.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Molecular mechanisms regulating cardiovascular remodeling by Adamts1

Ascending aorta dilation is a frequent cardiovascular complication of aortic valvular diseases, atherosclerosis, systemic arterial hypertension and genetic disorders. Ascending aorta aneurysms leading to dissections or rupture are major diseases affecting the aorta and are a common cause of premature deaths, such as Marfan syndrome or familial forms of non-syndromic thoracic aortic aneurysm and dissection. No clear explanation for the underlying molecular mechanisms has been found yet, nor is there an effective pharmacological treatment of these diseases. It is of paramount importance that our knowledge of the mediators of the diseases can be improved, so that pharmacological strategies can be designed in order to improve the quality and lifespan of the patients suffering these diseases. The MERC project seeks to clarify the molecular mechanisms that lead to ascending aorta aneurysms in the conditions mentioned. Previous work by the laboratory established >150 genes highly regulated by angiotensin II in vascular cells. One of such genes, Adamts1, was found to be a major mediator in vascular wall remodeling. Similar to mouse models of Marfan's disease, Adamts1+/- and Adamts1-/- mice present aortic dilation, aneurysms and medial degeneration. Specifically, NOS2 was found to be induced by Adamts1 deficiency. Based on those results, this project proposed to study the molecular mechanisms mediating these aortic diseases in mice, potentially providing a model for the study of the mechanisms in humans. Thus, the first aim of the project was to better characterize the roles of the isoforms of NOS in Adamts1-defficient mice and the signaling pathways downstream NOS2. A second aim was to determine potential common mechanisms of the aortopathies in Adamts1-defficient mice and Marfan mice, as well as in Marfan patients

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

Цел на проекта

Professor Redondo’s group has recently identified Adamts1 as one of the major mediators in vascular wall remodeling. They showed that Adamts1+/-, Adamts1-/- and KD-Adamts1 mice present aortic dilation, aneurysms, medial degeneration and hypotension, leading to the hypothesis that Adamts1 deficiency results in a new familial form of thoracic aortic aneurysm (FTAAD) potentially relevant in human aortic disease. They have also found that nitric oxide synthase (NOS) inhibitors reverse aortic dilation and medial degeneration in Marfan mice and Adamts1-deficient mice. The objective of my project is to study the molecular mechanisms mediating these aortic diseases in mice, and to specifically assess the role of nitric oxide (NO) and related signaling pathways, including those of Adamts1 and its substrates, in the medial degeneration and aortic dilation in both mouse models. I plan to identify potential targets common to both aortopathies and analyze them in patients with syndromic and non-syndromic aortic diseases. I think this project has a strong potential to identify therapeutic targets and prognostic or diagnostic markers for human cardiovascular diseases that constitute one of the major causes of mortality worldwide.

Оригинален текст от CORDIS (на английски).

Участници

CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) · MadridКоординаторИспания