Aortic Aneurysm and Dissection (AAD) are severe cardiovascular conditions with potentially lethal consequences such as aortic rupture. Existing studies suggest that liraglutide, a long-acting glucagon-like peptide receptor (GLP-1R) agonist, offers protective benefits across various cardiovascular diseases. However, the efficacy of liraglutide in mitigating AAD development is yet to be definitively elucidated. Ang II (Angiotension II) infusion of APOE^-/- mouse model with intraperitoneal injection of liraglutide (200 μg/kg) to study the role of GLP-1R in AAD formation. Bone Marrow Derived Macrophages (BMDM) and Raw264.7 were incubated with LPS, liraglutide, exendin 9-39 or LY294002 alone or in combination. SMC phenotype switching was examined in a macrophage and vascular smooth muscle cell (VSMC) co-culture system. An array of analytical methods, including Western Blot, Immunofluorescence Staining, Enzyme-LinkedImmunosorbent Assay, Real-Time Quantitative Polymerase Chain Reaction, RNA-seq, and so on were employed. Our investigation revealed a significant increase in M1 macrophage polarization and GLP-1R expression in aortas of AD patients and Ang II-induced AAD APOE^-/- mice. Administering liraglutide in APOE^-/- mice notably reduced Ang II-induced AAD incidence and mortality. It was found that liraglutide inhibits M1 macrophage polarization primarily via GLP-1R activation, and subsequently modulates vascular smooth muscle cell phenotypic switching was the primary mechanism. RNA-Seq and subsequent KEGG enrichment analysis identified CXCL3, regulated by the PI3K/AKT signaling pathway, as a key element in liraglutide's modulation of M1 macrophage polarization. Our study found liraglutide exhibits protective effects against AAD by modulating M1 macrophage polarization, suppressing CXCL3 expression through the PI3K/AKT signaling pathway. This makes it a promising therapeutic target for AAD, offering a new avenue in AAD management.

Aortic dissection (AD) is a life-threatening cardiovascular disease with a dismal prognosis. Inflammation plays an important role in AD. Oxylipins are bioactive lipids involved in the modulation of inflammation and may be involved in the pathogenesis and progression of AD. This study aims to identify possible metabolites related to AD. A total of 10 type A Aortic dissection (TAAD) patients, 10 type B Aortic dissection (TBAD) patients and 10 healthy controls were included in this study. Over 100 oxylipin species were identified and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. Our investigation demonstrated substantial alterations in 91 oxylipins between AD and healthy individuals. Patients with TAAD had 89 entries accessible compared to healthy controls. According to orthogonal partial least squares discriminant analysis (OPLS-DA), fitness (R²X = 0.362 and R²Y = 0.807, p = 0.03) and predictability (Q² = 0.517, p = 0.005) are the validation parameters between the two groups. Using multivariate logistic regression, 13-HOTrE and 16(17)-EpDPE were the risk factors in the aortic patients group compared to healthy people (OR = 2.467, 95%CI:1.256–7.245, p = 0.035; OR = 0.015, 95%CI:0.0002–0.3240, p = 0.016, respectively). In KEGG enrichment of differential metabolites, the arachidonic acid metabolism pathway has the most metabolites involved. We established a diagnostic model in distinguishing between AD and healthy people. The AUC was 0.905. Oxylipins were significantly altered in AD patients, suggesting oxylipin profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.

Dual antiplatelet therapy (DAPT) after coronary artery bypass grafting (CABG), although might be protective for ischemic events, can lead to varying degrees of bleeding, resulting in serious clinical events, including death. This study aims to develop accurate and scalable predictive tools for early identification of bleeding risks during the DAPT period post-CABG, comparing them with the PRECISE-DAPT score. Clinical data were collected from patients who underwent isolated CABG at Nanjing Drum Tower Hospital between June 2021 and December 2023. The dataset was split into derivation and validation cohorts at a 7:3 ratio. Machine learning models were developed to predict bleeding within six months post-CABG in DAPT patients and tested in a temporal external validation cohort. The SHapley Additive exPlanations method visualized variable importance regarding outcomes. The performance of the PRECISE-DAPT score was also validated in this cohort. Among 561 enrolled patients, 165 (29.4 %) experienced bleeding events, with 49 (8.7 %) cases being significant. In the validation cohort, eXtreme gradient boosting (XGB) achieved the highest area under the receiver operating characteristic curve (0.915) and precision-recall curve (0.692). Compared to PRECISE-DAPT, XGB showed no difference in AUROC (p = 0.808) but had a higher AUPRC (p = 0.009). In the temporal external validation cohort, the XGB model has an AUROC of 0.926 and an AUPRC of 0.703. We developed a dynamic high-accuracy bleeding risk calculator based on the XGB model and created a mobile-friendly QR code for easy access to this tool. Bleeding risk during DAPT in post-CABG patients can be reliably predicted using selected baseline features. The XGB model outperforms the Precise-Dapt model, showing better precision and recall.

Recent studies have underscored the cardioprotective properties of liraglutide. This research explores its impact on cardiac hypertrophy and heart failure following transverse aortic constriction (TAC). We found that liraglutide administration markedly ameliorated cardiac hypertrophy, fibrosis, and function. These benefits correlated with increased ANP expression and reduced activity in the calcineurin A/NFATc3 signaling pathway. Moreover, liraglutide mitigated ER stress and cardiomyocyte apoptosis, and enhanced autophagy. Notably, the positive effects of liraglutide diminished when co-administered with A71915, an ANP inhibitor, suggesting that ANP upregulation is critical to its cardioprotective mechanism.