Objective
Atherosclerosis and associated cardiovascular disease (CVD) is facilitated by several genetic and environmental risk factors, including hyper-cholesterolemia, diabetes, hypertension and smoking. Human diabetes is a multi-system disorder that results from progressive failure of insulin secretion and insulin resistance. Streptozotocin (STZ) has been widely used as a model to induce type 1 diabetes (insulin-dependent) as a result of its citotoxic activity in pancreatic b-cells. STZ treatment accelerates atherosclerosis in a wide spectrum of experimental animals, thus providing an appropriate model to identify molecular mechanisms involved in increased risk of CVD induced by type 1 diabetes. However, 90% of diabetic patients with premature CVD suffer from type 2 diabetes (non-insulin dependent) and the molecular mechanisms underlying this predisposition are largely unknown mainly because the lack of suitable experimental models.
In the present project, we will pursue two main objectives:
a) Generation and characterization of an animal model of atherosclerosis accelerated by type 2 diabetes. To this end, we will generate mice double deficient in apolipoprotein E and Insulin Receptor Substrate-2 (apoE-IRS-2-KO) and compare the kinetics of atherosclerosis versus mice single deficient in apoE (apoE-KO). Previous studies have shown that apoE-KO mice develop spontaneous atherosclerosis, and IRS-2-KO mice develop type 2 diabetes and display accelerated development of vascular obstructive lesions induced by mechanical injury to the arterial wall;
b) Identify changes in gene expression associated to atherosclerosis induced by hyper-cholesterolemia and diabetes.
To this end, we will compare DNA micro-array analysis from aortic tissue from apoE-KO and apoE-IRS-2-KO mice fed low-fat standard diet. These studies should improve our knowledge of the molecular mechanisms underlying atherosclerosis induced by hyper-cholesterolemia and type 2 diabetes, two main risk factors of CVD.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- social sciences sociology demography mortality
- medical and health sciences clinical medicine angiology vascular diseases
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences health sciences nutrition
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2004-MOBILITY-5
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
MADRID
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.