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Apelin‐13 treatment enhances the stability of atherosclerotic plaques
Author(s) -
FragaSilva Rodrigo A.,
Seeman Hugo,
Montecucco Fabrizio,
da Silva Analina R.,
Burger Fabienne,
CostaFraga Fabiana P.,
Anguenot Léa,
Mach François,
dos Santos Robson A. S.,
Stergiopulos Nikolaos,
da Silva Rafaela F.
Publication year - 2018
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12891
Subject(s) - apelin , medicine , endocrinology , cholesterol , oxidative stress , lesion , chemistry , apolipoprotein b , receptor , pathology
Abstract Background Apelin is an endogenous peptidergic system which modulates cardiovascular function. Recent studies pointed out a fundamental contribution of apelin on atherosclerosis development; however, such reports revealed contradictory data, and to date, it is difficult to accurately define a beneficial or deleterious role. To better understand apelin function on atherosclerosis, we aimed to investigate apelin‐13 treatment effects on atherosclerotic plaques composition. Design Apolipoprotein E gene‐deleted mice were fed on Western‐type diet for 11 weeks. Atherosclerotic plaque formation was induced in the carotid artery by a shear stress modifier device, which exposes the same vessel to distinct patterns of shear stress enabling the formation of plaques with different composition. Mice were treated with apelin‐13 (2 mg kg −1 day −1 ) or vehicle for the last 3 weeks. Results Apelin‐13 treatment did not alter the lipid content of low shear stress‐ and oscillatory shear stress‐induced plaques in the carotid. However, apelin‐13 greatly ameliorated plaque stability by increasing intraplaque collagen content and reducing MMP ‐9 expression. Furthermore, apelin‐13 decreased the infiltration of inflammatory cells (neutrophil and macrophage) and intraplaque reactive oxygen species content. Interestingly, apelin‐13 treatment reduced total cholesterol, LDL levels and free fatty acid serum levels, while HDL , triglycerides serum levels were not significantly changed. Conclusions Apelin‐13 treatment for 3 weeks did not alter the lesion size, but it significantly enhanced the stable phenotype of atherosclerotic plaques and improved serum lipid profile. These results indicate that activation of apelin system decreases plaque vulnerability.