Development of vascular smooth muscle cell models for investigating the role of CMKLR1/chemerin signalling in atherosclerosis

Abstract

Chemerin is a fat tissue-secreted protein that activates cellular processes though chemokine-like receptor 1 (CMKLR1) signalling. Serum chemerin is positively correlated to atherosclerosis severity, however the functional role of chemerin in atherosclerosis remains unknown. The study goal was to assess the role of chemerin/CMKLR1 signalling in human and mouse vascular smooth muscle cell (VSMC) migration and proliferation (important stages of atherosclerotic plaque formation). A protocol for differentiating human adipose-derived stem cells into SMCs was investigated. Morphological VSMC-characteristics were observed, as was chemerin and CMKLR1 expression, however further VSMC phenotype confirmation is required. Therefore, a second approach used primary aortic mouse VSMCs from CMKLR1-expressing and CMKLR1-deficient mice. Mouse VSMCs expressed chemerin and CMKLR1, and secreted low levels of chemerin. Low chemerin concentrations enhanced VSMC migration via CMKLR1 signalling and high concentrations inhibited migration via a CMKLR1-independent mechanism. This data suggests the involvement of chemerin/CMKLR1 signalling in atherogenic VSMC processes.