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.

Background: Myocardial injury-related cardiogenic shock (MICS) is significantly associated with poor outcomes in patients after cardiac surgery. Herein, we aimed to investigate the risk factor for postoperative MICS. Methods: We performed a case-control study on 792 patients undergoing cardiac surgery from 2016 to 2019, including 172 patients with postoperative MICS and 620 age- and sex-matched controls. MICS was defined as composite criteria: a cardiac index of < 2.2 L/m²/min, arterial lactate levels of > 5 mmol/L at the end of the surgery, a vasoactive-inotropic score of > 40 at the end of the surgery, and a cardiac troponin T (cTnT) level of > 0.8 µg/L on postoperative day 1 (POD1) with an increase of > 10% on POD 2. Results: A total of 4671 patients who underwent cardiac surgery in our hospital between 2016 and 2019 were included; of these, 172 (3.68%) had MICS and the remaining 4499 did not. For investigating the risk factors, we selected 620 age- and sex-matched controls. In the univariate analysis, MICS was significantly associated with death (P < 0.05), extracorporeal membrane oxygenation (P < 0.05), continuous renal replacement therapy (P < 0.01), and ventricular arrhythmias (P < 0.05). Multivariable logistic regression analysis revealed that diabetes mellitus (OR:8.11, 95% CI: 3.52–18.66, P < 0.05) and a cardiopulmonary bypass (CPB) time of > 2 h (OR: 3.16, 95% CI: 1.94–5.15, P < 0.05) were associated with postoperative MICS. Moreover, long-time administration of preoperative calcium channel blocker (CCB) was associated with a less incidence of MICS (OR: 0.11, 95% CI: 0.05–0.27, P < 0.05). Conclusions: Postoperative MICS is significantly associated with poor outcomes. Diabetes mellitus and long CPB time are associated with MICS. Preoperative CCB administration is associated with less incidence of MICS.

Abdominal aortic aneurysm (AAA) is a lethal vascular disorder characterized by aortic dilation and medial degeneration, with no effective pharmacological interventions currently available. Pathological vascular smooth muscle cell (VSMC) phenotypic switching and apoptosis drive AAA progression. Mangiferin, a bioactive xanthone from Mangiferia indica l., exhibits anti-inflammatory and cardiovascular protective properties that could potentially alleviate AAA. This study aims to investigate mangiferin's therapeutic effects on AAA and elucidate its molecular mechanisms. Apolipoprotein E-deficient (ApoE^-/-) mice were infused with angiotensin II (Ang II) to induce AAA and subsequently treated with low-dose (10 mg/kg/d) or high-dose (50 mg/kg/d) mangiferin. Aortic pathology was assessed via histological analysis, zymography, and immunofluorescence. VSMC phenotypic switching and apoptosis were examined through western blotting and immunofluorescence, while their molecular regulation by mangiferin was investigated using a combined approach of RNA-sequencing, molecular docking, cellular thermal shift assay, and functional studies. Compared to low dose-mangiferin, high dose-mangiferin reduced the incidence of AAA, aneurysm diameter enlargement, and elastin degradation in the AAA model. Mangiferin pretreatment also attenuated VSMC phenotypic switching and apoptosis in Ang II-stimulated VSMCs compared to non-pretreatment. Mechanistically, mangiferin directly bound to STAT3 at Lys591 via hydrogen bonding in the SH2 domain, inhibiting its Tyr705 phosphorylation and dimerization, and eventually blocking its nuclear translocation. This in turn suppressed KLF5 transcriptional activity and pro-aneurysmal target expression. Furthermore, both pharmacological and genetic activation of the STAT3-KLF5 axis abrogated mangiferin's protective effects in the AAA model. This study is the first to demonstrate that mangiferin inhibits AAA by targeting the STAT3-KLF5 axis to stabilize VSMC contractility and survival, placing mangiferin as a novel natural therapeutic candidate for AAA.

Background: We sought to explore the relationship between dexmedetomidine as an anesthetic adjuvant in cardiac surgery and postoperative complications and length of stay (LOS) in the cardiac intensive care unit (CICU). Methods: We conducted a retrospective study of patients aged 18 years and older who underwent heart valve surgery between October 2020 and June 2022. The primary endpoint of the study was major postoperative complications (cardiac arrest, atrial fibrillation, myocardial injury/infarction, heart failure) and the secondary endpoint was prolonged CICU LOS (defined as LOS > 90th percentile). Multivariate logistic regression analysis was performed for variables that were significant in the univariate analysis. Results: A total of 856 patients entered our study. The 283 patients who experienced the primary and secondary endpoints were included in the adverse outcomes group, and the remaining 573 were included in the prognostic control group. Multivariate logistic regression analysis revealed that age > 60 years (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.23–2.31; p < 0.01), cardiopulmonary bypass (CPB) > 180 min (OR, 1.62; 95% CI, 1.03–2.55; p = 0.04) and postoperative mechanical ventilation time > 10 h (OR, 1.84; 95% CI, 1.35–2.52; p < 0.01) were independent risk factors for major postoperative complications; Age > 60 years (OR, 3.20; 95% CI, 1.65–6.20; p < 0.01), preoperative NYHA class 4 (OR, 4.03; 95% CI, 1.74–9.33; p < 0.01), diabetes mellitus (OR, 2.57; 95% CI, 1.22–5.41; p = 0.01), Intraoperative red blood cell (RBC) transfusion > 650 ml (OR, 2.04; 95% CI, 1.13–3.66; p = 0.02), Intraoperative bleeding > 1200 ml (OR, 2.69; 95% CI, 1.42–5.12; p < 0.01) were independent risk factors for prolonged CICU length of stay. Intraoperative use of dexmedetomidine as an anesthetic adjunct was a protective factor for major complications (odds ratio, 0.51; 95% confidence interval, 0.35–0.74; p < 0.01) and prolonged CICU stay. (odds ratio, 0.37; 95% confidence interval, 0.19–0.73; p < 0.01). Conclusions: In patients undergoing heart valve surgery, age, duration of cardiopulmonary bypass, and duration of mechanical ventilation are associated with major postoperative complication. Age, preoperative NYHA classification 4, diabetes mellitus, intraoperative bleeding, and RBC transfusion are associated with increased CICU length of stay. Intraoperative use of dexmedetomidine may improve such clinical outcomes.

Insulin resistance (IR) is a key driver of cardiovascular disease (CVD), the leading cause of global mortality. This study evaluated the prognostic value of two surrogate IR indices—the McAuley index and the Metabolic Score for Insulin Resistance (METS‐IR)—for predicting all‐cause and CVD mortality. Data from 22,308 NHANES participants with established CVD (1999–2018) was analyzed. Outcomes were all‐cause and CVD mortality. Cox proportional hazards models and restricted cubic splines assessed associations, while machine learning methods (random forest, XGBoost, CoxBoost, DeepHit) evaluated predictive performance. Model interpretability was assessed using SHapley Additive exPlanations (SHAP). Over a median 9.2‐year follow‐up, 3484 deaths occurred, including 1093 from CVD. A higher McAuley Index was inversely associated with risk, with each 1‐unit increase predicting a 9.2% reduction in all‐cause and 11.3% reduction in CVD mortality. Higher METS‐IR values were associated with increased mortality. Restricted cubic spline analysis confirmed significant U‐shaped relationships. Across nine models, the Cox model demonstrated the best performance (C‐index: 0.87 for all‐cause and 0.85 for CVD mortality), with time‐dependent AUCs consistently above 0.8. SHAP analysis highlighted the McAuley Index and METS‐IR as leading predictors. The McAuley Index and METS‐IR are robust, independent predictors of all‐cause and CVD mortality. Their integration with interpretable machine learning enhances risk stratification, underscoring the role of metabolic dysfunction and central adiposity in long‐term outcomes. These indices may help identify high‐risk patients who could benefit from targeted interventions.

Oxidative stress plays a central role in the development of peripheral artery disease (PAD), yet composite indices quantifying its impact remain underutilized. The oxidative balance score (OBS), integrating dietary and lifestyle exposures, may offer a comprehensive approach to vascular risk stratification. We analyzed data from 7249 U.S. adults in NHANES 1999–2004 to examine the association between OBS and PAD, defined by an ankle‐brachial index ≤ 0.9. Multivariable logistic regression and restricted cubic spline models were used to assess both linear and nonlinear associations. Twelve machine learning models were constructed to predict PAD status; the top‐performing model (GLMNet) was interpreted using SHapley Additive exPlanations (SHAP) to identify key predictors. Higher OBS levels were significantly associated with reduced PAD prevalence (fully adjusted OR per unit increase: 0.963; 95% CI: 0.944–0.983; p < 0.001), with a U‐shaped dose–response curve. The inverse association remained consistent across most subgroups. In sensitivity analyses focusing on diabetic individuals, the total OBS was not significantly associated with PAD, but the lifestyle component of OBS remained protective. SHAP analysis identified total folate intake, physical activity, and serum cotinine as the most influential predictors, while classic antioxidants such as vitamin C and vitamin E had limited predictive value. Integrating conventional regression and interpretable machine learning, this study demonstrates a nonlinear, inverse association between oxidative balance and PAD. OBS may serve as a practical composite biomarker for vascular risk profiling, with particular relevance for lifestyle‐based interventions in high‐risk populations.