Journal of Cardiovascular Translational Research最新文献

Oral dysbiosis, particularly through periodontal disease, links strongly to cardiovascular risks by driving chronic inflammation and microbial translocation. Key pathogens invade vascular tissues, triggering systemic cytokines and metabolites that damage endothelial function and promote atherosclerosis. This creates a vicious cycle where oral inflammation worsens heart disease progression. Clinical interventions like intensive periodontal therapy show promise, reducing blood pressure and inflammatory markers in at-risk patients, much like established lifestyle changes. Salivary microbial profiles emerge as early warning signs for vascular issues and poor outcomes. This review bridges epidemiology, mechanisms, trials, biomarkers, and practical strategies, clarifying causal gaps through structured evidence analysis. Future multi-omics research and standardized approaches will refine oral health's role in heart disease prevention, offering actionable public health steps.

Glutaminase-1 (GLS1) converts glutamine to glutamate, fueling anaplerosis, redox defense, and biosynthesis. We synthesize animal, cellular, and human (bulk/single-cell) data to define cell- and stage-specific roles of GLS1 in atherosclerosis and to outline translational opportunities. In early disease, GLS1 drives vascular smooth muscle proliferation, endothelial sprouting, and inflammatory macrophage activation, promoting plaque growth and neovascularization. In advanced plaques, GLS1 sustains fibrous-cap VSMC survival, endothelial barrier function, and macrophage efferocytosis, limiting necrosis and enhancing stability; excessive glutamate may favor calcification. We also connect GLS1 to vascular senescence and ferroptosis. We propose precision use of GLS1 modulation: a proof-of-concept strategy is short-term telaglenastat (CB-839) after angioplasty to curb neointimal hyperplasia, guided by glutamine-PET and biomarkers to avoid destabilizing mature plaques. GLS1 emerges as a tunable metabolic checkpoint whose effects depend on cell state and disease stage; judicious, time-limited modulation could complement lipid-lowering and anti-inflammatory therapies in cardiovascular disease.

Despite advances in heart failure management, current therapies largely focus on symptom relief and slowing disease progression, without reversing or preventing the underlying condition. As cardiovascular diseases remain a leading cause of mortality, developing curative treatments is an urgent goal. Advances in understanding the molecular mechanisms of heart failure, alongside insights into pathways that drive cardiac regeneration have opened new avenues for gene therapies aimed at restoring cardiac function. While several gene therapy candidates have advanced to clinical trials, their outcomes have been inconsistent, underscoring the challenge to translating preclinical success into clinical efficacy. In this review, we examine the current landscape of gene therapy strategies for ischemic heart failure, emphasize the importance of robust preclinical models in bridging the gap from bench to bedside, and highlight emerging regenerative approaches that aim to repair damaged myocardium and restore cardiac function.

Growing evidence implicates solute carrier (SLC) superfamily in atherosclerosis (AS) pathogenesis. This study identified SLC22A3 as a novel AS biomarker and therapeutic target using multi-omics analysis. Integrating WGCNA and machine learning (LASSO, SVM-RFE, XGBoost, Random Forest) on bulk RNA-seq (GSE43292) pinpointed SLC22A3. External datasets (GSE28829, GSE163154) confirmed significant SLC22A3 downregulation in AS (P < 0.001) and high diagnostic accuracy (AUC > 0.9). SMR analysis revealed a causal genetic link between SLC22A3 expression and reduced AS risk (P < 0.05, OR = 0.512 (95% CI: 0.280-0.939))). scRNA-seq showed SLC22A3 specifically expressed in smooth muscle cells (SMCs), significantly reduced in symptomatic patients. Molecular docking and molecular dynamics simulation nominated six FDA-approved drugs as potential SLC22A3-targeting therapeutics. Experimental validation further confirmed the significant downregulation of SLC22A3 at both mRNA and protein levels. SLC22A3 is a promising diagnostic biomarker and therapeutic target for AS, functionally linked to SMCs.

The increasing popularity of E-cigarettes among young adults has raised concerns about their health effects, particularly on the circadian system, which regulates critical physiological processes. This study examined how vaping influences circadian proteins and inflammatory markers, comparing these effects to those in cardiovascular disease patients. Blood samples from 254 participants, non-vaping controls (n = 90), regular vapers (n = 86), and cardiovascular patients (n = 78), were analyzed for circadian proteins (Melatonin, BMAL1, PER1, PER2, CRY1, CRY2) and inflammatory/oxidative stress markers (IFN-γ, MDA). Vaping significantly decreased Melatonin, PER1, PER2, CRY1, and CRY2, while BMAL1 remained unchanged. Elevated IFN-γ and MDA levels indicated increased inflammation and oxidative stress in vapers. Vaping induces circadian disruption patterns similar to cardiovascular disease, suggesting a potential mechanism linking e-cigarette use to increased cardiovascular risk.

Mitral regurgitation (MR) is the most common valvular disease in developed countries. Many patients with functional MR (FMR) are inoperable due to high surgical risk, and effective transcatheter options are limited. Radiofrequency (RF) ablation can contract connective tissue. To assess the feasibility, safety, and efficacy of Biorefine, a novel transcatheter RF ablation system for mitral annulus remodeling without implants, in a preclinical ovine model. Twelve sheep underwent transseptal RF ablation of the posterior mitral annulus under 3D echocardiographic and fluoroscopic guidance. Mitral geometry and coaptation were evaluated acutely (n = 4), at 58 days (n = 4), and 178 days (n = 4). Histology assessed tissue effects. All procedures were complication-free. Eleven of 12 animals showed ≥ 15% annular area reduction (mean 21.8%), ≥ 10% A-P diameter reduction (mean 15%), and 71.9% mean coaptation increase. Histology confirmed localized fibrosis (≤ 3 mm) without off-target injury. Biorefine appears safe, durable, and implant-free for FMR.

Cardiovascular disease (CVD) and neuropsychiatric manifestations are common in patients with Systemic Lupus Erythematosus (SLE), often sharing a vascular origin with endothelial dysfunction central to their development. The endothelium plays a critical role in regulating systemic and cerebral blood flow and influencing end-organ damage in SLE. In this review, we summarize foundational and recent studies linking vascular dysfunction to CVD and neuropsychiatric outcomes, emphasizing the roles of endothelial activation, endothelial progenitor cells, blood-brain barrier dysfunction, and vascular autoantibodies. We also highlight animal models that facilitate the study of vascular and cerebral manifestations, clarifying the interconnected contributions of endothelial health to SLE-related organ damage. Finally, we discuss emerging therapeutic strategies aimed at restoring endothelial function to improve cardiovascular and neuropsychiatric outcomes in SLE.

Heart failure remains a major global health burden, with mitochondrial dysfunction recognized as a key contributor to its onset and progression. This review highlights three critical regulators of mitochondrial integrity phosphocreatine (PCr), cyclophilin D (CypD), and signal transducer and activator of transcription 3 (STAT3) and their coordinated roles in cardiac function. PCr is vital for sustaining myocardial energy balance, particularly under metabolic stress. CypD controls the mitochondrial permeability transition pore, regulating cell death pathways that contribute to cardiac injury. Beyond its classical nuclear actions, STAT3 supports mitochondrial respiration, biogenesis, and resistance to oxidative damage. Evidence reveals a functional interplay among these regulators, forming a protective network that preserves mitochondrial performance. Disruption of this network promotes energetic failure, mitochondrial injury, and heart failure progression. Targeting PCr metabolism, CypD activity, and STAT3 signaling may represent a promising therapeutic approach to enhance mitochondrial resilience and improve clinical outcomes in heart failure patients.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disorder with heterogeneous presentations, making diagnosis and management highly dependent on imaging and clinical expertise. This narrative review examines how artificial intelligence (AI) and machine learning (ML) are transforming FMD care. AI-enhanced imaging, particularly convolutional neural network-based analysis, improves detection of the characteristic "string-of-beads" pattern on CT angiography, magnetic resonance angiography, and ultrasound, although FMD-specific validation remains limited. ML models facilitate risk stratification, prediction of disease progression, and early identification of complications such as aneurysms and stroke by integrating clinical, imaging, and genomic data. AI-driven clinical decision support systems further enable personalized treatment selection through pharmacogenomic insights and robot-assisted interventions. Despite promising real-world applications, challenges persist, including limited large-scale datasets, workflow integration, regulatory barriers, and algorithmic bias affecting underrepresented populations. Future advances in explainable AI, federated learning, and digital health integration may enable a shift toward predictive, patient-centered FMD management.

Silent Myocardial Infarction (SMI) is a clinically underrecognized phenotype along the myocardial infarction continuum that progresses without anginal symptoms. Its prevalence in diabetes, chronic kidney disease, and the elderly reflects contributions from neuropathy, autonomic dysfunction, and neurogenic silencing. Emerging evidence indicates that SMI reflects a biologically biased phenotype within the myocardial infarction continuum shaped by immune-metabolic and neurogenic modulation rather than representing a distinct entity. Biomarkers such as sCD36, galectin-3, sST2, and GDF-15 capture fibrotic and inflammatory remodeling, while NETosis-linked markers (CitH3, MPO-DNA) highlight thrombo-inflammation. Lipidomic stressors, including ceramides and β-hydroxybutyrate, further define ischemic burden. Spatial omics and single-cell analyses identify enrichment of immune-regulatory macrophage programs associated with restrained inflammation without establishing the causality for symptom absence. A tiered approach-biomarker screening followed by imaging-supports risk stratification. This review integrates mechanistic and translational insights, proposing a pragmatic framework for early diagnosis and biologically aligned treatment of SMI.