Journal of Cardiovascular Translational Research最新文献

This study explored the association between 19 peripheral artery disease (PAD)-associated variants and PAD severity. We classified PAD cases into 4 groups with increasing levels of severity based on age of PAD diagnosis and surgical status. Genetic association analysis for PAD severity and markers was conducted using REGENIE, and a 19-variant polygenic risk score (PRS) was developed to further evaluate the associations with severity subtypes. Two SNPs (rs4722172 and rs505922) showed stronger odds ratios (ORs) with more severe subtypes. The 19-variant PRS was significantly higher in surgical compared to non-surgical groups (OR = 1.14, 95% CI: 1.08, 1.20; p-value = 5.85 × 10^-7) while no significant difference for non-premature and premature PAD (OR = 0.98, 95% CI: 0.9, 1.07, p-value = 0.64). This same pattern was observed in the subjects from Generations dataset. Our findings demonstrate that PAD-associated SNPs may also be associated with PAD severity as assessed by surgical intervention and age of onset (or diagnosis).

Myocardial ischemia-reperfusion injury (MIRI) is an unresolved clinically fatal complication in the management of acute myocardial infarction (AMI). Growth arrest and DNA damage-inducible gene 45 Gamma (GADD45G) plays a vital role in the regulation of MIRI. However, the underlying mechanisms remain unclear. GADD45G and SP1 expression were upregulated in hypoxia/reoxygenation (H/R)-treated H9C2 cells. H/R treatment repressed H9C2 cell viability, and induced apoptosis, oxidative stress, and inflammatory response. Moreover, GADD45G deficiency could relieve H/R-triggered H9C2 cell injury. In mechanism, SP1 was a transcription factor of GADD45G and activated the transcription of GADD45G via binding to its promoter region. Besides, SP1 knockdown alleviated MI/R-induced pathological damage in the myocardial tissue of rats by regulating GADD45G. In conclusion, SP1 could promote H/R-induced cardiomyocyte injury and MI/R-caused rat myocardial tissue pathological injury by increasing GADD45G, providing a promising therapeutic target for MIRI treatment.

Ischemic mitral regurgitation (IMR) commonly complicates pPCI in STEMI patients. GDF11, a protective cardiovascular factor, may influence IMR progression and prognosis. Among 310 STEMI patients, 126 with recent normal echocardiography underwent pPCI with pre-procedural GDF11 testing. Cox regression, ROC analysis, and Spearman's correlation assessed GDF11's predictive value for IMR exacerbation and cardiac function. Lower GDF11 predicted IMR worsening (HR = 0.982, P = 0.004; AUC = 0.744, P < 0.001). High GDF11 patients had reduced IMR progression (P = 0.0013) and heart failure risk (P = 0.0003). GDF11 correlated with LVEF and left atrial changes (P < 0.05). Serum GDF11 independently predicts IMR exacerbation and post-pPCI heart failure, serving as a prognostic biomarker in STEMI.

Testosterone (TES) has complex roles in cardiovascular disease, influencing not only atherosclerosis development in general, but also atherosclerosis-related processes associated with hypertension, cholesterol metabolism, vascular calcification, and arterial stiffness. This review examines TES's effects, particularly its atheroprotective role in various mice and minipig model systems and cell cultures. TES modulates the renin-angiotensin system (RAS), contributing to hypertension and vascular dysfunction, but its deprivation can mitigate these effects. TES also impacts cholesterol metabolism by regulating liver X receptor (LXRα) pathways, promoting both cholesterol clearance and synthesis. Moreover, TES is involved in vascular calcification via androgen receptor (AR) signalling, a process that contributes to arterial stiffness, especially in females. The review highlights gaps in understanding TES's specific molecular mechanisms in cardiovascular disease, emphasising the need for further research to explore sex-specific responses and potential therapeutic interventions.

Ischemic heart disease is a leading cause of global morbidity and mortality, yet early diagnosis and targeted therapies remain limited. Exosomes, small extracellular vesicles carrying nucleic acids, proteins, and lipids, mediate intercellular communication and show promise for diagnostic and therapeutic use due to their stability, biocompatibility, and targeted delivery. Circulating exosomal profiles reflect myocardial pathology, enabling early detection, risk stratification, and monitoring. Exosomes from mesenchymal stem cells, immune cells, endothelial cells, and other stem cells exert cardioprotective effects. This review summarizes advances in exosome-based diagnostics and therapies and highlights their potential as biomarkers and innovative treatments.

This study aims to integrate lesion-specific pericoronary adipose tissue (PCAT) radiomics analysis with existing clinical and imaging methods under the guidance of CT-derived fractional flow reserve (CT-FFR), to develop and validate an interpretable machine learning (ML) prediction model for patients with type 2 diabetes complicated by coronary artery disease (CAD). The performance of ML algorithms across different predictive models was compared using the area under the receiver operating characteristic curve (AUC). In the validation cohort, the XGBoost algorithm within the combined model achieved an AUC value of 0.908, outperforming the best algorithm in the traditional model (AUC = 0.834) and radiomics model (AUC = 0.840). Meanwhile, the Shapley algorithm highlights the additional incremental value of radiomic features. Our model enhances the predictive ability and provides clinicians with a comprehensive tool, facilitating early intervention for high-risk individuals and proactive secondary prevention strategies, which may potentially improve clinical outcomes.

Coronary obstruction following transcatheter aortic valve-in-valve implantation (VIV-TAVI) carries a high mortality risk. This in-vitro study assessed coronary perfusion in a high-risk VIV-TAVI scenario. A patient deemed at high-risk and treated with preventive Chimney stenting was selected as case study. A 3D-printed aortic root model was fabricated from pre-operative imaging and used to replicate the patient's VIV-TAVI setting. A CoreValve-Evolut-23 was implanted within a Trifecta-19 at five depths, with commissural alignment and 60° misalignment, to explore procedural variability and associated risk margins. The model was tested in a pulsatile mock loop with a coronary perfusion simulator. Flow and pressure were recorded pre- and post-VIV-TAVI under physiological conditions. Across all tested configurations, VIV-TAVI didn't significantly impair left or right coronary flows. The recommended depth optimized hemodynamic valve performance. Findings suggest refining coronary obstruction risk stratification in VIV-TAVI to improve decision-making regarding preventive interventions.

Three-dimensional (3D) printing has rapidly evolved as a transformative technology in cardiovascular medicine, offering capabilities for anatomical modelling, surgical planning, and the development of biocompatible implants. This review synthesizes evidence from peer-reviewed studies to provide a comprehensive overview of 3D printing technologies, materials, and their clinical applications in cardiovascular fields, including myocardial tissue engineering, valve replacement, and vascular modelling. Emphasis is placed on patient-specific modelling, integration of bio-printing technologies, and recent clinical demonstrations of improved surgical precision and reduced implant rejection. Drawing on 28 primary sources, this review identifies current benefits and challenges of 3D printing in cardiovascular care, highlights emerging trends, and proposes future directions for research and clinical translation.

Acute coronary syndrome, driven by vulnerable plaque (VP) instability, is a major cause of cardiovascular mortality. Current diagnostic methods for VPs are limited by invasiveness or low specificity, highlighting the need for non-invasive biomarkers. Using single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from coronary artery disease (CAD) patients with VPs and controls, we identified circulating T cell-platelet aggregates (TPAs) significantly enriched in VP patients and linked to plaque instability via pro-inflammatory pathways. Through high dimensional weighted gene co-expression network analysis, we discovered TPAs' hub genes and demonstrated their role in plaque destabilization. Furthermore, employing machine learning, including Boruta, least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE), we screened for five blood biomarkers that can serve as diagnostic indicators for VPs. Our study demonstrates that TPAs are critically involved in VPs formation. Furthermore, we identified EPHB6, STAT1, RPL23, IKZF3 and AHCY as potential circulating biomarkers for non-invasive detection of VPs.

Tricuspid regurgitation (TR) is a highly morbid and often untreated valvular heart disease. New devices are under development to address this unmet need, necessitating valid models to test their efficacy. Aim of this study was to assess feasibility and reliability of pulmonary artery banding (PAB) as a pathological acute model of functional TR. Eight pigs underwent right thoracotomy, with an umbilical tape placed around the main pulmonary trunk, followed by controlled reduction of the pulmonary artery lumen via a tourniquet system. No animals died during the procedure. After PAB, right ventricular (RV) mean pressure, RV basal and mid-diameter and tricuspid septo-lateral diameter significantly increased (+ 97%, + 23%, + 32%, + 20%, p < 0.01 for all). Consequently, TR was at least moderate-to-severe in all the animals and these modifications remained stable for up to one hour. PAB therefore represents a reliable, one-step model of functional TR ideal to test the efficacy of new tricuspid devices.