Mistry LN, Agarwal S, Bhandarkar SD
… +3 more, Sharma V, Jaiswal H, More S
J Cardiovasc Transl Res
· 2026 Mar · PMID 41817867
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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 cyt...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.
J Cardiovasc Transl Res
· 2026 Mar · PMID 41811615
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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 GL...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.
J Cardiovasc Transl Res
· 2026 Mar · PMID 41811538
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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...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.
Yu Y, Wang L, Wang T
… +4 more, Zhang Y, Su X, Dai X, Mo X
J Cardiovasc Transl Res
· 2026 Mar · PMID 41806154
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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 WGCN...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.
J Cardiovasc Transl Res
· 2026 Mar · PMID 41803320
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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. Radi...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.
Alzu'bi A, Abu-El-Rub E, Khaswaneh RR
… +9 more, Al-Zubaidi M, Almomani W, Alenaizat A, Ayyash AH, Alragheb A, Alshannag A, Ahmad E, Elaarag M, Al-Zoubi RM
J Cardiovasc Transl Res
· 2026 Mar · PMID 41801528
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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...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.
J Cardiovasc Transl Res
· 2026 Mar · PMID 41795008
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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....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.
Qaed E, Liu W, Aldahmash W
… +3 more, Mahyoub MA, Elshafei HA, Tang Z
J Cardiovasc Transl Res
· 2026 Mar · PMID 41790403
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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...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.
Hamza A, Faiz M, Iftikhar A
… +10 more, Badal B, Qamar S, Ali E, Usman M, Talha M, Un Nisa N, Mujtaba A, Butt A, Talat NF, Ashraf A
J Cardiovasc Transl Res
· 2026 Mar · PMID 41790300
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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 examine...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.
Pethani Y, Pethani N, Pethani D
… +3 more, Shah R, Shah D, Shah J
J Cardiovasc Transl Res
· 2026 Mar · PMID 41784746
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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...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.
Marano P, Washington K, Chazarin B
… +16 more, Sundararaman N, Raedschelders K, Maughan J, Obrutu O, Tjoe B, Herscovici R, Moy P, Shufelt C, Rutledge T, Polyak A, Joung S, Liu Y, Cheng S, Wei J, Van Eyk JE, Merz CNB
J Cardiovasc Transl Res
· 2026 Feb · PMID 41760974
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Takotsubo syndrome (TTS) is an under-recognized form of acute-onset heart failure typically precipitated by stress. While recovery of cardiac function is described over the course of weeks, adverse outcomes after apparen...Takotsubo syndrome (TTS) is an under-recognized form of acute-onset heart failure typically precipitated by stress. While recovery of cardiac function is described over the course of weeks, adverse outcomes after apparent recovery are increasingly recognized. However, the pathophysiology of non-acute manifestations remains poorly understood. We used mass-spectrometry-based discovery proteomics from remotely collected non-acute dried blood microsamples to perform a case-control study in 62 participants with a prior TTS episode (median of 2.24 years prior to sample collection) and 47 reference controls. We quantified 398 unique proteins, and found that agnostic clustering techniques showed separation between TTS and reference control samples. This represents the first proteomic characterization of non-acute TTS. Pathway analysis of the 52 differentially regulated proteins demonstrated enrichment of proteins involved in complement activation, nitric oxide signaling, and with antioxidant activity. These enriched pathways may be suggestive of a persistent cardiomyopathy resulting from or predisposing to TTS.
Madandar E, Zarinfar Y, Namazi MH
… +4 more, Sohrabifar N, Namazi MJ, Eslami V, Khaheshi I
J Cardiovasc Transl Res
· 2026 Feb · PMID 41758284
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Early-onset ST-segment elevation myocardial infarction (STEMI) in individuals under 50 is an increasing concern. Identifying new biomarkers could improve early diagnosis and intervention. In this case-control study, we i...Early-onset ST-segment elevation myocardial infarction (STEMI) in individuals under 50 is an increasing concern. Identifying new biomarkers could improve early diagnosis and intervention. In this case-control study, we investigated endothelial-related long non-coding RNAs (lncRNAs) MANTIS, NORAD, RNCR3, and SENCR as potential diagnostic markers. Blood samples from 200 young STEMI patients and 200 age-matched controls were analyzed using real-time PCR to evaluate lncRNA expression. NORAD and MANTIS levels were significantly reduced in STEMI patients (p < 0.001). MANTIS displayed the strongest association (AUC = 0.92), while NORAD demonstrated a moderate association (AUC = 0.68). SENCR and RNCR3 showed no significant differences between groups. The downregulation of MANTIS and NORAD suggests their potential roles as biomarkers in early-onset STEMI. MANTIS, in particular, may enhance risk stratification and treatment. Further research is warranted to validate these findings in broader populations.
Liao K, Dong Q, Mo C
… +3 more, Yang G, Huang B, Luo S
J Cardiovasc Transl Res
· 2026 Feb · PMID 41739272
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Mitral regurgitation (MR) is a significant risk factor for heart failure, yet existing rodent models face limitations in invasiveness and reproducibility. This study established a novel percutaneous, ultrasound-guided ra...Mitral regurgitation (MR) is a significant risk factor for heart failure, yet existing rodent models face limitations in invasiveness and reproducibility. This study established a novel percutaneous, ultrasound-guided rat model of MR to overcome these constraints. Thirty male Sprague-Dawley rats underwent echocardiography-guided mitral valve injury, allocated to severe MR (40-70% regurgitation), massive MR (> 70%), or sham groups. Serial echocardiographic assessments were performed at baseline, 30 min, and 2, 4, and 8 weeks post-procedure, with histological validation of myocardial fibrosis. The technique achieved 100% success with no acute mortality and enabled precise titration of regurgitation severity. Both MR groups exhibited progressive, body size-independent cardiac remodeling. Speckle-tracking revealed basal-segment-predominant longitudinal strain reduction, correlating with histologically confirmed peri-annular fibrosis. Survival was significantly lower in massive MR (40% vs. 90%, p = 0.006). This minimally invasive model reliably replicates human MR pathophysiology with high reproducibility and precise severity control, providing a robust platform for mechanistic investigation.
J Cardiovasc Transl Res
· 2026 Feb · PMID 41724871
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Glucagon-like peptide-1 (GLP-1) is a hormone mainly produced by intestinal L cells after meal, and its main functions include enhancing glucose-dependent insulin secretion, promoting insulin biosynthesis, inhibiting gluc...Glucagon-like peptide-1 (GLP-1) is a hormone mainly produced by intestinal L cells after meal, and its main functions include enhancing glucose-dependent insulin secretion, promoting insulin biosynthesis, inhibiting glucagon secretion, inhibiting gastrointestinal activity and regulating appetite. In recent years, GLP-1, besides its well-known hypoglycemic effects, has been shown to have beneficial effects in the cardiovascular field, but the precise molecular mechanism is not yet fully understood. GLP-1 receptor (GLP-1R) is a class B G-protein-coupled receptor (GPCR), which is widely distributed in the cardiovascular system. This review aims to summarize the GLP-1R dependent signaling pathways in GLP-1 cardiovascular protection and related researches, such as the GLP-1R structure, distribution and expression. Moreover, we also discussed the development of GLP-1R agonist (GLP-1RA) therapies in cardiovascular field.
J Cardiovasc Transl Res
· 2026 Feb · PMID 41724860
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Myocardial ischemia-reperfusion injury (MIRI) involves tissue damage following restoration of blood flow. Stearoyl-CoA desaturase 1 (SCD1), associated with metabolic disorders, may contribute to MIRI. This study investig...Myocardial ischemia-reperfusion injury (MIRI) involves tissue damage following restoration of blood flow. Stearoyl-CoA desaturase 1 (SCD1), associated with metabolic disorders, may contribute to MIRI. This study investigated the mechanism of SCD1 in MIRI. A rat ischemia/reperfusion (I/R) model was established by ligating the left anterior descending coronary artery. The hypoxia/reoxygenation (H/R) model was used to simulate in vitro I/R. 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry were performed for histopathological analysis of rat heart tissues. The ferroptosis indicators were detected using commercial kits and Western blot. Lactylation and ubiquitination of SCD1 were detected by Western blot. I/R increased tissue damage and SCD1 expression. In addition, SCD1 inhibition attenuated ferroptosis in H/R cells and I/R hearts. H/R induced ferroptosis via promoting lactylation modification in H9c2 cells. Mechanistically, lactylation of SCD1 at K208 stabilized its protein stability and activated Wnt/β-Catenin signaling to promote ferroptosis in H9c2 cells. In vivo, SCD1 silencing inhibited the MIRI. SCD1 lactylation drove ferroptosis in MIRI by regulating Wnt/β-Catenin signaling, offering potential therapeutic insights.
J Cardiovasc Transl Res
· 2026 Feb · PMID 41709029
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The development of blood-wetted artificial organs is limited by thrombosis on synthetic biomaterial surfaces. In contrast, the endothelium of the vasculature creates a natural barrier to both thrombosis and pannus growth...The development of blood-wetted artificial organs is limited by thrombosis on synthetic biomaterial surfaces. In contrast, the endothelium of the vasculature creates a natural barrier to both thrombosis and pannus growth. Consequently, efforts have been made to endothelialize synthetic biomaterials used in blood-wetted devices. Therefore, this study was undertaken to provide a numerical model to simulate the inhibitory effects of EC-derived nitric oxide (NO) on platelet deposition. An existing multi-constituent continuum model of thrombosis was amended to incorporate shear-dependent generation of NO as an anticoagulant. A simulation was performed of blood flow through a bipartite parallel plate channel having an endothelialized upstream layer followed by a pro-coagulant collagen surface downstream. The simulation showed that endothelial-derived NO inhibited downstream platelet deposition, reducing thrombus growth and creating a thrombus-free zone immediately downstream. This enhanced simulation model of thrombosis provides insights into factors that may guide future endothelialization of artificial organs and other blood-wetted devices.