BACKGROUND: Uncertainties persist about whether to aggressively and effectively treat tricuspid regurgitation (TR) during mitral valve (MV) surgery. REVIEW METHODS: Systematic literature searches were performed in five databases to collect all relevant studies published before May 2022 on whether the tricuspid valve was treated during MV surgery. Separate meta-analyses were performed on data from unmatched studies and randomized controlled trials (RCT)/adjusted studies. MAIN RESULTS: A total of 44 publications were included, of which eight were RCT studies and the rest were retrospective studies. There was no difference in 30-day mortality [odds ratio (OR): 1.00, 95% CI: 0.71-1.42, OR: 0.66, 95% CI: 0.30-1.41)] or overall survival [hazard ratio (HR): 1.01, 95% CI: 0.85-1.19, HR: 0.77, 95% CI: 0.52-1.14] in unmatched studies and RCT/adjusted studies. Late mortality (OR: 0.37, 95% CI: 0.21-0.64) and cardiac-related mortality (OR: 0.36, 95% CI: 0.21-0.62) were lower in the tricuspid valve repair (TVR) group in the RCT/adjusted studies. In the unmatched studies, overall cardiac mortality (OR: 0.48, 95% CI: 0.26-0.88) was lower in the TVR group. In the late TR progression analysis, the late TR progression was lower among patients in the concomitantly intervened tricuspid group, and patients in the untreated tricuspid group were prone to TR progression in both studies (HR: 0.30, 95% CI: 0.22-0.41, HR: 0.37, 95% CI: 0.23-0.58). CONCLUSIONS: TVR concomitant with MV surgery is most effective in patients with significant TR and dilated tricuspid annulus, especially those with a significantly reduced risk of distant TR progression.

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.