Role of Chemerin/ChemR23 axis as an emerging therapeutic perspective on obesity-related vascular dysfunction

Abstract

Sufficient epidemiological investigations demonstrate that there is a close correlation between obesity and vascular dysfunction. Nevertheless, specific mechanisms underlying this link remain currently unclear. Given the crucial and decisive role of vascular dysfunction in multitudinous diseases, various hypotheses had been proposed and numerous experiments were being carried out. One recognized view is that increased adipokine secretion following the expanded mass of white adipose tissue due to obesity contributes to the regulation of vascular function. Chemerin, as a neo-adipokine, whose systemic level is elevated in obesity, is believed as a regulator of adipogenesis, inflammation, and vascular dysfunction via binding its cell surface receptor, chemR23. Hence, this review aims to focus on the up-to-date proof on chemerin/chemR23 axis-relevant signaling pathways, emphasize the multifarious impacts of chemerin/chemR23 axis on vascular function regulation, raise certain unsettled questions to inspire further investigations, and explore the therapeutic possibilities targeting chemerin/chemR23.

Keywords: Adipokine; ChemR23; Chemerin; Obesity; Vascular dysfunction; White adipose tissue.

Fig. 1

Distinctions of the three receptors for chemerin. ChemR23, GPR1 and CCRL2 are cell-surface receptors, and all of them have a high affinity for chemerin. ChemR23 leads to strong signaling and internalization of the chemerin–receptor complex. GPR1 leads to weak signaling but also displays equal internalization as chemR23. CCRL2 does not signal nor internalizes but might pass on chemerin to functional chemR23 of nearby cells

Fig. 2

The potential pathogenic effects of chemerin/chemR23 axis on vascular dysfunction and cardiovascular diseases. The schematic figures indicate that chemerin/chemR23 axis leads to vascular dysfunction through diversified pathways, including ECs (enhanced proliferation and migration, increased inflammation, decreased NO production and augmented oxidative stress), VSMCs (enhanced proliferation and migration, increased inflammation, excessive apoptosis, augmented oxidative stress) and PVAT dysfunction (enhanced chemerin secretion and increased chemR23 expression), which further results in various vascular-related diseases

Fig. 3

Unsettle experimental questions