Project Details
Description
Atherosclerosis is part of the cardiovascular diseases and represents the most important cause of death worldwide. Each year not less than 17,5 million people (of which 2 million in Europe) die of cardiovascular diseases. Monocytes/macrophages are involved in all stage of the pathology of atherosclerosis, ranging from the initiation (recruitment) to the progression (accumulation and differentiation to foam cells) until the rupture of the thrombus.
Recently Angiotensin IV (Ang IV) has been shown to be protective in animal models for atherosclerosis. Ang IV is a bio-active peptide fragment of the cardiovascular hormone Angiotensin II. It has a number of interesting biological effects such improvement of memory and learning, by its interaction with the AT4 receptor. This receptor has been identified as the insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3); a membrane-bound zinc-dependent aminopeptidase. Besides the cerebral effects of Ang IV, a peripheral role of Ang IV/IRAP in the modulation of inflammation has recently been suggested. This potential pro-inflammatory effects is very interesting with respect to our recent findings in which we showed the presence of AT4-binding sites in both mouse macrophage cell lines as well as ex vivo primary macrophages (non published data in the MBFA research team).
Starting from these observations and the possible role of Ang IV in atherosclerose, we intend to further study in depth the relation between Ang IV, atherosclerosis and macrophages. The research project comprises three parts: (i) characterization and regulation of IRAP in macrophages, (ii) study of the cellular and functional consequences of the interaction between IRAP and Ang IV and analogues, (iii) exploration whether this modulation can be useful in the development of a novel treatment strategy of atherosclerosis.
Recently Angiotensin IV (Ang IV) has been shown to be protective in animal models for atherosclerosis. Ang IV is a bio-active peptide fragment of the cardiovascular hormone Angiotensin II. It has a number of interesting biological effects such improvement of memory and learning, by its interaction with the AT4 receptor. This receptor has been identified as the insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3); a membrane-bound zinc-dependent aminopeptidase. Besides the cerebral effects of Ang IV, a peripheral role of Ang IV/IRAP in the modulation of inflammation has recently been suggested. This potential pro-inflammatory effects is very interesting with respect to our recent findings in which we showed the presence of AT4-binding sites in both mouse macrophage cell lines as well as ex vivo primary macrophages (non published data in the MBFA research team).
Starting from these observations and the possible role of Ang IV in atherosclerose, we intend to further study in depth the relation between Ang IV, atherosclerosis and macrophages. The research project comprises three parts: (i) characterization and regulation of IRAP in macrophages, (ii) study of the cellular and functional consequences of the interaction between IRAP and Ang IV and analogues, (iii) exploration whether this modulation can be useful in the development of a novel treatment strategy of atherosclerosis.
Acronym | IWT479 |
---|---|
Status | Finished |
Effective start/end date | 1/10/09 → 30/09/13 |
Keywords
- Applied Biology
Flemish discipline codes in use since 2023
- Biological sciences
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