Endothelial CCRL2 induced by disturbed flow promotes atherosclerosis via chemerin-dependent β2 integrin activation in monocytes.

AIMS: Chemoattractants and their cognate receptors are essential for leucocyte recruitment during atherogenesis, and atherosclerotic plaques preferentially occur at predilection sites of the arterial wall with disturbed flow (d-flow). In profiling the endothelial expression of atypical chemoattractant receptors (ACKRs), we found that Ackr5 (CCRL2) was up-regulated in an endothelial subpopulation by atherosclerotic stimulation. We therefore investigated the role of CCRL2 and its ligand chemerin in atherosclerosis and the underlying mechanism. METHODS AND RESULTS: By analysing scRNA-seq data of the left carotid artery under d-flow and scRNA-seq datasets GSE131776 of ApoE-/- mice from the Gene Expression Omnibus database, we found that CCRL2 was up-regulated in one subpopulation of endothelial cells in response to d-flow stimulation and atherosclerosis. Using CCRL2-/-ApoE-/- mice, we showed that CCRL2 deficiency protected against plaque formation primarily in the d-flow areas of the aortic arch in ApoE-/- mice fed high-fat diet. Disturbed flow induced the expression of vascular endothelial CCRL2, recruiting chemerin, which caused leucocyte adhesion to the endothelium. Surprisingly, instead of binding to monocytic CMKLR1, chemerin was found to activate β2 integrin, enhancing ERK1/2 phosphorylation and monocyte adhesion. Moreover, chemerin was found to have protein disulfide isomerase-like enzymatic activity, which was responsible for the interaction of chemerin with β2 integrin, as identified by a Di-E-GSSG assay and a proximity ligation assay. For clinical relevance, relatively high serum levels of chemerin were found in patients with acute atherothrombotic stroke compared to healthy individuals. CONCLUSIONS: Our findings indicate that d-flow-induced CCRL2 promotes atherosclerotic plaque formation via a novel CCRL2-chemerin-β2 integrin axis, providing potential targets for the prevention or therapeutic intervention of atherosclerosis

First report of Feline Calicivirus (FCV) infection in stray cats in northeast China

Abstract To improve our understanding of Feline calicivirus (FCV) infection in cats in Northeast China, 1584 serum samples from 974 domestic cats and 610 stray cats were collected between 2012 and 2015. The samples were tested for FCV antibodies using a commercially available ELISA kit. The results revealed an overall seroprevalence of 37.56% (595/1584), a seroprevalence in domestic cats of 32.85% (320/974) and a seroprevalence in stray cats of 45.08% (275/610). Risk factor analysis indicated that species was the only risk factor for the presence of FCV (OR=1.678, 95% CI=1.362-2.066, P&lt;0.001); age, season, region and gender were not risk factors. This is the first report of FCV infection in stray cats in China, and the results of this study can aid in FCV infection control in the felidae family.</jats:p