Introduction:
Atherosclerosis remains one of the main cause of death worldwide and substantial efforts have been made to identify novel approaches to improve the management of this disorder. Apelin is an endogenous peptidergic family with essential role on the cardiovascular hemostasis and pathologies. Recent studies pointed out a fundamental contribution of Apelin system on atherosclerosis development; however, such reports revealed contradictory data, and to date, it is difficult to accurately define the beneficial or deleterious role of Apelin in atherosclerosis.
Objective:
To better understand the role of Apelin system on atherosclerosis, we aimed to investigate the actions of Apelin-13 treatment on atherosclerotic plaques composition, focusing on features of plaque vulnerability.
Methods:
Apolipoprotein E gene-deleted mice (n=40) were fed with western-type diet for 11 weeks. Atherosclerotic plaque formation was induced in the carotid artery by a shear stress modifier device, which exposed the vessel to distinct patterns of shear stress, resulting in plaque formation with different composition. The mice were treated with Apelin-13 (2 mg/Kg/day) or vehicle for the last 3 weeks of experimental period.
Results:
Apelin-13 treatment did not change atherosclerotic plaque size in the aorta, neither altered the lipid content of low shear stress and oscillatory shear stress-induced plaques in the carotid. However, Apelin-13 remarkably ameliorated plaque stability by increasing intraplaque collagen content, which was associated with a reduction of MMP-9 expression. Furthermore, Apelin decreased cell infiltration (neutrophil and macrophage) and intraplaque reactive oxygen species content. Interestingly, Apelin-13 treatment reduced total cholesterol, LDL levels and free fatty acids serum levels, while HDL, triglycerides serum levels were not significantly changed.
Conclusion:
Apelin-13 treatment for 3 weeks did not alter the lesion size, but significantly enhances the stable phenotype of atherosclerotic plaques and improved serum lipid profile. These results indicate that activation of Apelin system enhances plaque stability.
The role of macrophage transcription factor MafB in atherosclerotic plaque stability
