izvor podataka: poirot


Poremećena vazorelaksacija i endotelno-leukocitna interakcija (ELI) u razvoju aterosklerotskih lezija

Impaired Vasorelaxation and Endothelial-Leukocyte Interaction (ELI) in Development of Atherosclerotic Lesions

Opis projekta

High salt (HS) diet suppresses the renin-angiotensin system (RAS) and is known risk factor for hypertension and cardiovascular diseases. Furthermore, HS diet has a direct effect on endothelial activation under atherogenic shear stress, promoting the endothelial-leukocyte interactions in ApoE-/-mice.Oxidative stress underlies inflammatory processes in atherosclerotic plaque formation. Our previous studies demonstrated that RAS suppression by HS diet underlies impaired endothelium-dependant vasorelaxation due to increased oxidative stress and due to the shift in the production of vasoreactive metabolites of arachidonic acid. Infusion of subpressor doses of angiotensin II restored normal vasorelaxation. However, involvement of the RAS in development of early atherosclerosis is only emerging. In this project we will test the hypothesis that restoration of the RAS (by infusions of subpressor doses of angiotensin II) decreases endothelial activation and abolishes endothelial-leukocyte interactions (ELI) by eliminating oxidative stress and the production of proinflammatory metabolites of arachidonic acid. We will use normotensive Sprague-Dawley (SD) rats that exhibit suppression of the RAS with HS intake and in TFF3-/- transgenic mice. TFF3-/- mice are complete novelty in this research approach, and promising new model for studying the atherosclerotic lesion formation and proinflammatory cytokine synthesis, due to their protective phenotype of favorable ratio of ?6/?-3 fatty acids and modified metabolism of arachidonic acid. Aim 1: to elucidate the effect of RAS restoration on the mechanisms of flow-mediated responses in animals on HS diet. Aim 2: to determine the effect of RAS restoration on endothelial cells and leukocytes interactions. The results may provide evidence for the shift in the paradigm that the RAS is always detrimental to circulation and support the new paradigm of crucial role of normally modulated RAS in prevention of atherosclerotic lesion formation

Ključne riječi

Znanstveno-istraživački projekti

V-ELI Athero




nije evidentirano

HRK 981.988

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