Ling Yang

The growing comorbidity between cardiovascular and neuropsychiatric disorders presents a major global health challenge. This reciprocal interaction worsens patient prognosis and hinders the diagnosis and treatment of these comorbid conditions. In recent years, the concept of the "gut-heart-brain axis" has highlighted the central pathogenic and therapeutic role of the gut microbiota in linking these distal systems. This review therefore aims to clarify this axis and to explore how specific gut microbiota metabolites modulate this bidirectional physiological interaction. We have integrated recent research to elucidate how gut microbiota dysbiosis regulates cardiovascular-neuropsychiatric comorbidities through the following convergent pathways: gut barrier disruption leading to metabolic endotoxemia; NLRP3 inflammasome activation; adaptive immunity shifting towards Th17 cell dominance and suppressing regulatory T cells; hypothalamic-pituitary-adrenal axis overactivation; and autonomic nervous system dysfunction. We critically reviewed microbiome-targeted interventions, noting that although the existing literature provides reliable epidemiological associations and proof of concept in animal models, definitive causal relationships in human populations remain insufficiently confirmed. Establishing such causal relationships between specific microbial metabolites and the outcomes of chronic cardiovascular or neuropsychiatric diseases will require rigorous longitudinal and interventional studies.

Background: Left posterior fascicular ventricular tachycardia (LPF-VT) is considered the most common type of fascicular ventricular tachycardia. False tendons (FTs) are reported to be common in patients with LPF-VT and may contribute to the pathogenesis of this condition. However, LPF-VT cases with congenital septal structural abnormalities have not been reported. Case summary: This case report investigated an 86-year-old woman diagnosed with LPF-VT who underwent radiofrequency ablation. The preoperative transthoracic echocardiography (TTE) results indicated no anatomic abnormalities. During the procedure, the intracardiac echocardiography (ICE) revealed a fissure within the ventricular septum. The successful ablation site was precisely located at the left orifice of this fissure. To improve treatment efficacy, the catheter was advanced into the fissure to continue ablation. One month postoperatively, the patient presented with mild shortness of breath after activity. The TTE revealed a 15× 16-mm iatrogenic ventricular septal defect (VSD) with a pulmonary artery pressure (PAP) of 48 mmHg. Percutaneous VSD closure resolved the symptoms, and the PAP returned to normal. During the follow-up period, no recurrence of palpitations or dyspnoea was observed. Discussion: Macro-re-entry has been suggested as the mechanism of LPF-VT, as FTs can provide an electro-anatomical substrate for LPF-VT. In the present case, the re-entrant circuit of LPF-VT may be associated with the rare anatomic anomaly, although a definitive link remains unestablished. Additionally, extreme caution should be exercised during catheter manipulation to prevent iatrogenic injuries.

Cluster of differentiation 38 (CD38) is a widely expressed transmembrane glycoprotein in various human tissues and cells with vital biological roles in the heart and brain, possessing both NADase and cyclase activities. It is involved in regulating heart and brain functions through various pathways, including calcium (Ca²⁺) signaling nicotinamide adenine dinucleotide (NAD⁺) content, oxidative stress, inflammation and immune response. Its combined role in heart-brain coexisting diseases suggests that inhibiting CD38 has a protective effect on cardiovascular diseases (CVD) and neurological disorders. This review aims to discuss the expression patterns, regulatory mechanisms, and CD38 signaling pathways in the heart and brain. In conclusion, CD38 is implicated in the shared pathogenesis of heart-brain diseases, providing novel insights for future research.

Background: Stress hyperglycemia ratio (SHR) has been associated with poor outcomes in patients with acute myocardial infarction (AMI). Modified SHR (mSHR) is defined as the highest SHR observed within the first 24 h of admission. However, the association between mSHR and early cardiovascular complications (ECC) following AMI is unclear. Methods: This multicenter observational study incorporated retrospective and prospective analyses across two independent cohorts. The discovery and validation cohorts each included consecutive AMI patients admitted to intensive care units. The blood glucose and hemoglobin A1c levels were used to calculate mSHR. The primary outcome was the occurrence of ECC during the hospital stay. Results: In the discovery cohort, ECC occurred in 322 (23.9%) of 1,349 patients, and mSHR was independently associated with ECC (adjusted odds ratio: 1.164; 95% confidence interval (CI): 1.124–1.206; P < 0.001). Machine learning approaches identified mSHR as the most important feature. In the validation cohort, 303 patients were divided into three groups according to mSHR tertiles. Modified Poisson regression analysis showed that patients with mSHR ≥ 1.202 (tertile 3) had a significantly higher risk of ECC compared to those in tertiles 1–2 (adjusted risk ratio: 2.337; 95% CI: 1.479–3.693; P < 0.001). The results of multivariate analysis were consistent before and after applying inverse probability of treatment weighting. Conclusion: In AMI patients, mSHR is an accurate risk-stratification tool for identifying ECC. It may provide exploratory evidence to optimize current glycemic control strategies and early discharge pathways.

The comorbidity of cardiovascular diseases (CVDs) and mental disorders (MD) has become a significant challenge in modern medicine, severely affecting patients’ quality of life and prognosis. The heart-brain axis, a bidirectional pathway connecting the central nervous system and the cardiovascular system, plays a critical role in the comorbidity mechanisms of CVDs and MD. In recent years, brain-derived neurotrophic factor (BDNF) has emerged as a key molecule in the study of CVDs and MD. By binding with high affinity to TrkB receptors and activating various signaling pathways, BDNF exerts multiple functions in both the nervous and cardiovascular systems. BDNF may participate in the pathogenesis of CVDs combined with MD through multiple mechanisms such as regulating inflammatory responses, oxidative stress (OS), and the hypothalamic-pituitary-adrenal (HPA) axis, making it a promising new target for future diagnosis and treatment. This review systematically summarizes the mechanisms by which BDNF functions in heart-brain comorbidity, particularly its multifaceted influence on inflammation, OS, and neuroendocrine regulation. Additionally, we discuss the clinical application prospects of BDNF in disease diagnosis and treatment, as well as progress in related drug development. A deeper understanding of BDNF’s role in the heart-brain axis will provide new insights and strategies for the prevention, diagnosis, and treatment of CVDs and MD.

Coronary Artery Disease (CAD) is the most common cardiovascular disease worldwide, threatening human health, quality of life and longevity. Aging is a dominant risk factor for CAD. This study aims to investigate the potential mechanisms of aging-related genes and CAD, and to make molecular drug predictions that will contribute to the diagnosis and treatment. We downloaded the gene expression profile of circulating leukocytes in CAD patients (GSE12288) from Gene Expression Omnibus database, obtained differentially expressed aging genes through “limma” package and GenaCards database, and tested their biological functions. Further screening of aging related characteristic genes (ARCGs) using least absolute shrinkage and selection operator and random forest, generating nomogram charts and ROC curves for evaluating diagnostic efficacy. Immune cells were estimated by ssGSEA, and then combine ARCGs with immune cells and clinical indicators based on Pearson correlation analysis. Unsupervised cluster analysis was used to construct molecular clusters based on ARCGs and to assess functional characteristics between clusters. The DSigDB database was employed to explore the potential targeted drugs of ARCGs, and the molecular docking was carried out through Autodock Vina. Finally, single-cell data (GSE159677) of arterial intima was used to further explore the expression of aging signature genes in different cell subpopulations. We identified 8 ARCGs associated with CAD, in which HIF1A and FGFR3 were up while NOX4, TCF7L2, HK3, CDK18, TFAP4, and ITPK1 were down in CAD patients. Based on this, CAD patients can be divided into two molecular clusters, among which cluster A mainly involves functional pathways such as ECM receptor interaction and focal adhesion; cluster B mainly involves functional pathways such as amimo sugar and nucleotide sugar metabolism and pyrimidine metabolism. In addition, the molecular docking results showed that retinoic acid and resveratrol had good binding affinity with targets genes. Further single-cell analysis results showed that NOX4, TCF7L2, ITPK1, and HIF1A were specifically expressed in different types of cells in atherosclerotic tissues. Our study identified several ARCGs that may be involved in the pathogenesis and progression of CAD. Further, retinoic acid and resveratrol were potential candidate molecule drugs for inhibiting these targets.

Purpose This study aimed to investigate the effects of transcutaneous auricular vagus nerve stimulation (ta-VNS) on heart failure with preserved ejection fraction (HFpEF) and explore the related mechanisms. Methods Sprague–Dawley rats were fed a high-fat diet and N^[w]-nitro-L-arginine methyl ester to establish an HFpEF model. Ta-VNS was achieved by electrical stimulation of the auricular concha. Histology and echocardiography were used to identify changes in cardiac function and pathology. RNA sequencing was used to explore the underlying mechanism. RT‒PCR, WB, and immunofluorescence staining were used to determine the effects of ta-VNS on macrophage polarization. In vitro, RAW264.7 cells were induced into the M1 or M2 type. An α7nAChR agonist and an α7nAChR inhibitor were used to explore the effects of α7nAChR on macrophage polarization. Finally, an α7nAChR inhibitor was used to determine whether the therapeutic effects of ta-VNS are related to α7nAChR. Results In vivo, ta-VNS alleviated cardiac dysfunction and pathological remodeling in rats with HFpEF. RNA sequencing demonstrated that the protective effects of ta-VNS on HFpEF were related to macrophage-mediated inflammatory responses. Ta-VNS decreased the expression of M1-type macrophage markers but increased the expression of M2-type markers. In vitro studies revealed that the α7nAChR agonist decreased the polarization of macrophages toward the M1 type, whereas the α7nAChR inhibitor reduced the polarization toward the M2 type. Furthermore, the α7nAChR inhibitor abolished the protective effects of ta-VNS on macrophage polarization and myocardial remodeling in rats with HFpEF. Conclusion Ta-VNS ameliorated HFpEF-induced cardiac remodeling, which was associated with the modulation of macrophage polarization.

Sarcopenia was recognized to be one of the common comorbidities in heart failure (HF). The sarcopenia index (SI), based on serum creatinine to cystatin C ratio, was developed as a simple tool to evaluate skeletal muscle mass but has not been well-studied in the correlation of left ventricular ejection fraction (LVEF). The aim of this study is to analyze the SI in patients with HF, especially patients with HF with preserved ejection fraction (HFpEF), and to develop a prediction model for HFpEF. The training cohort included 229 hospitalized patients with HF and 73 healthy controls (HCs) from the Third Affiliated Hospital of Soochow University between December 2019 and February 2022. An additional 78 patients with HF hospitalized at the same hospital between March 2022 to June 2023 were considered as an external validation cohort. Binary logistic regression model was used to analyze the influence factors of HFpEF. A prediction model was constructed and optimized based on the least absolute shrinkage and selection operator (LASSO), displayed by Nomogram and verified internally by Bootstrap with 500 resamples. SI was significantly different between the HF and HC groups (67.95 ± 13.07 vs. 98.57 ± 31.51) and had a significant negative correlation with LVEF. Multivariate logistic regression demonstrated that SI (OR 0.948, 95% CI 0.914—0.983, P = 0.004) was independently associated with HFpEF. The area under the curve (AUC) for the nomogram constructed based on SI was 0.902. The calibration curve was approximately distributed along the reference line in Bootstrap and the decision curve analysis demonstrated significantly better net benefit in the model. The external validation proved the good predictive performance of the model. Lower SI is an independent factor associated with hospitalized patients with HF, especially patients with HFpEF. A prediction nomogram based on SI has good predictive power for HFpEF. The study was registered with the China Clinical Trials Centre Registry (registration number: ChiCTR2200063401).

There is no effective treatment for diabetes-related atrial remodeling currently. This study aimed to investigate the effects of renal denervation (RDN) on diabetes-related atrial remodeling and explore the related mechanisms. A type 2 diabetes mellitus model was established by high-fat diet feeding and low-dose streptozotocin injection in Sprague‒Dawley rats. After successful modeling, the diabetic rats were randomly assigned to two groups according to whether they were subjected to RDN or sham RDN surgery. At the end of the experiment, cardiac function and structure were evaluated by echocardiography and histology, respectively. Mitochondrial morphology, function and mitochondrial dynamics were assessed by multiple methods. Mdivi1 was used to verify the mechanism by which RDN improves atrial remodeling. In the 10th week, diabetic rats exhibited obvious atrial remodeling, including atrial enlargement and diastolic dysfunction. Pathological staining showed that diabetic rats had cardiomyocyte hypertrophy and interstitial fibrosis in atrial tissues. In terms of mitochondrial morphology and function, diabetic rats exhibited fragmented mitochondria, reduced adenosine triphosphate production and decreased mitochondrial membrane potential levels. Abnormal mitochondrial dynamics in diabetic rats were characterized by the inhibition of mitochondrial fusion, excessive mitochondrial fission, and the suppression of mitophagy. However, RDN effectively ameliorated diabetes-induced pathological atrial remodeling. In addition, RDN significantly improved mitochondrial morphological and functional abnormalities and corrected the disorders of mitochondrial dynamics. Furthermore, the protective effects of RDN against atrial remodeling were related to the regulation of mitochondrial dynamics. RDN prevented diabetes-induced atrial remodeling. These protective effects might be related to improvements in mitochondrial dynamics.