Cardiovascular (CV) diseases are the major source of morbidity and mortality in the EU with annual costs of € 169 billion. The control of hypertension and prevention of left ventricular (LV) hypertrophy and fibrosis, which could interrupt the CV continuum, still remain insufficient world-wide. A substantial part of current therapies modulate the renin-angiotensin system (RAS) and decrease the unfavorable stimulation of angiotensin type 1 receptors (AT1R). Results of the host group indicate that many of AT1R effects are opposed by type 2 receptor (AT2R) activation. AT2R are up-regulated in several pathologies, making targeting of AT2R effective specifically in disease. The investigation of long-term effects of direct AT2R activation on hypertension and CV remodeling was allowed only recently by the discovery of AT2R agonist, compound 21. Fellows results suggest, that the pineal hormone and antioxidant, melatonin, prevents fibrosis and can be especially useful in combination with RAS modulation. We aim to investigate the effects of 5-week administration of compound 21, melatonin and their combination in L-NAME hypertensive rats on CV remodeling and relevant protein expression pattern. Advanced, interdisciplinary techniques from physiology to molecular biology will be implemented. The findings should indicate whether the exciting AT2R targeting is a promising approach to CV diseases and whether the use of a novel drug combination can preserve myocardial structural homogeneity. This project will yield important scientific and clinical implications and provide an outstanding training, guaranteed by excellent researcher in charge. Proposed training will unfold researcher’s creativity, networking and other complementary skills and promote his scientific maturity and independence necessary to create an own research group. Possible reintegration of the researcher with his enhanced scientific output will increase the competitiveness in his country of origin.
Field of science
- /natural sciences/biological sciences/molecular biology
Call for proposal
See other projects for this call