A protective role for CGRP in the development of atherosclerosis in apoE knockout mice

抄録

Atherosclerosis is driven by inflammatory reactions that are shared with the innate immune system. Calcitonin gene related peptide (CGRP) is a potent vasodilator peptide and it is widely distributed in central and peripheral nerve. Recent studies have shown that CGRP can be produced by immune cells such as macrophages following stimulation. However, it is unclear whether CGRP is involved in atherosclerosis development. Here, we investigated whether CGRP has a role in the development of atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Newly generated double-knockout apoE-/-/CGRP-/- mice and control apoE-/- mice were fed a high-fat diet from 5 to 10-week-old. ApoE-/-/CGRP-/- mice demonstrated exacerbated atherosclerotic lesion severity with increase total cholesterol level. As a potential mechanism accounting for plaque progression in ApoE-/-/CGRP-/- mice, macrophage migration or adhesion was further investigated and only migration was significantly increased by CGRP depletion. These results suggest that CGRP deletion exacerbated atherosclerosis in apoE-/- mice. Macrophages migration was identified as potential mediators of this effect.