Project description
Preventive strategies against cardiometabolic diseases
Obesity and diabetes affect cardiovascular health and contribute to the development of cardiometabolic diseases (CMD). To prevent CMD occurrence, the EU-funded PREVENT-2024 project proposes to develop interventions for people with established endocrine abnormalities. These will be based on molecules that exhibit deregulation in obesity and diabetes, namely the hormone neurotensin, vasopressin and adrenomedullin. Scientists will evaluate strategies that inhibit the upregulation and control the levels of these molecules in animal models and human clinical trials. Alongside data from omics studies, the project results will help predict and prevent CMD.
Objective
Increasing occurrence of obesity and diabetes is the major threat to cardiovascular health of our century. Whereas the field is saturated with “omics” strategies aimed at improving prediction of cardiometabolic disease (CMD), mechanism-orientated prevention strategies, which is what the population calls for, are lacking. We here propose three completely new and high-risk strategies to prevent CMD in large subsets of the population, who have elevated risk due to measurable endocrine abnormalities.
SUBPROJECT 1: We test if the increased CMD risk linked to high levels of the intestinal fat absorption and storage promoting hormone neurotensin (NTS), can be improved by: (A) blockade of NTS using monoclonal antibodies in mice and (B) inhibition of NTS secretion and intestinal fat uptake with the drug orlistat in humans.
SUBPROJECT 2: High plasma levels of vasopressin (VP) (present in 25% of the population) is a strong risk factor for later CMD and the dominating cause of high VP is low water intake. We therefore test if the elevated CMD risk in subjects with high VP can be reduced by increasing water intake in a large 12-month randomized trial of 1.5 L water supplementation vs control therapy.
SUBPROJECT 3: Aderenomedullin (ADM), whose endothelial secretion is enhanced in obesity, has beneficial effects on the intravascular wall but in the extravascular space, to which it diffuses freely, it may promote diabetes. We investigate how long-term increase and decrease of levels of bioactive ADM in the intra- and extravascular compartments, respectively, affect atherosclerosis and glucose metabolism in mice. In humans we test if a monoclonal antibody, which traps ADM in the circulation (while still allowing it to bind to its endothelial receptors) and drains it from the extravascular space, improves vascular function and glucose metabolism.
We provide completely novel, mechanism-orientated and near-future applicable strategies for primary prevention of CMD.
Fields of science
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Funding Scheme
ERC-ADG - Advanced GrantHost institution
22100 Lund
Sweden