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.

The Regulatory Roles of Chemerin-Chemokine-Like Receptor 1 Axis in Placental Development and Vascular Remodeling During Early Pregnancy

“…Patients suffering from hypertension and PE showed significantly higher serum chemerin concentrations ( Cetin et al, 2017 ; Xie and Liu, 2022 ). The increased placental chemerin was also found in the villi of preeclamptic women ( Xu et al, 2014 ; Tan et al, 2022 ).…”

Role of Chemerin in Cardiovascular Diseases

“…Chemerin was found to decrease eNOS generation and stimulate NO breakdown, resulting in overall NO reduction in endothelial cells. It has been speculated that additional mechanisms, such as eNOS uncoupling and reduced NO-dependent cGMP signalling, could contribute to chemerin-mediated endothelial dysfunction [ 117 , 120 ].…”

“…Chemerin was shown to increase the expression of various endothelial inflammatory factors such as IL-6, TNFα, and CRP, which results in abnormal endothelial secretion, blood vessel wall inflammation, and increased monocyte attachment to endothelial cells [ 124 , 125 , 126 ]. Interestingly, inflammatory cytokines such as TNF-α, IL-1β, and IL-6 were found to modulate chemerin effects by increasing the expression of CMKLR1 receptor in endothelial cells [ 120 ]. In human coronary artery endothelial cells, elevated circulating chemerin concentration is associated with increased expression of intercellular adhesion molecule 1 (ICAM-1) and E-selectin, which are regarded as typical markers of vascular endothelial activation [ 127 ].…”

“…Studies show that short-term in vitro treatment of VSMCs with chemerin (20 min) increased the proliferation and migration capacity of VSMCs via MAPK and Akt/ERK signalling [ 130 , 131 ], the endothelin-1 dependent pathway [ 132 ], and increased autophagy [ 133 ]. Interestingly, prolonged incubation of VSMCs with chemerin (6 h) led to VSMC’s apoptosis [ 126 ], suggesting that chemerin may exert different functions at different stages of vascular remodelling and dysfunction [ 120 ]. In addition, increased ROS accumulation and elevated expressions of inflammatory cytokines such as IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1) were observed in chemerin-treated VSMCs, suggesting that chemerin can induce VSMC dysfunction by augmenting oxidative stress and promoting inflammation [ 126 , 134 , 135 , 136 , 137 ].…”

Chemerin Forms: Their Generation and Activity

“…The role of chemerin in pediatric and gestational diabetes will not be discussed here, although there is good evidence of its involvement [ 100 , 101 ]. There are many reports describing chemerin levels along with other adipokines in various cohorts showing that chemerin levels are associated with disorders involved with energy balance [ 81 , 82 , 92 , 102 ]. Those reports are in agreement that levels of circulating chemerin are higher in people with obesity.…”