Chronic intermittent hypoxia (CIH) constitutes the primary pathophysiological disturbance in obstructive sleep apnoea (OSA), recognised as an independent risk factor for cardiovascular disease. The protective peptide alamandine (ALA), emerging as a novel component of the renin-angiotensin system, holds potential for elucidating molecular mechanisms underlying OSA-associated atrial fibrillation (AF). This study demonstrates that ALA treatment downregulates the expression of molecules associated with the GRP78/ATF6/CHOP pathway and pyroptosis-related proteins, while simultaneously mitigating atrial electrophysiological and structural remodelling and reducing susceptibility to AF. These findings suggest that the cardioprotective effects of ALA may be mediated through regulation of ERS and pyroptosis-related pathways, providing preliminary experimental evidence for its potential application in AF therapy. However, the precise molecular mechanisms require further functional validation.
The pathogenesis and progression of cardiometabolic diseases (CMD) are intricately linked to epigenetic regulation mediated by chromatin remodeling. Modifications to histones, such as post-translational acetylation and methylation, along with DNA methylation, alter chromatin structure and accessibility, resulting in transient or irreversible alterations in gene expression without accompanying changes in the DNA sequence. Herein, we outline the trajectory of epigenetic chromatin remodeling across various tissues, focusing on the liver-heart axis and the crosstalk between various epigenetic mechanisms in CMD pathogenesis and progression. We provide a list of drugs that target crucial epigenetic enzymes for CMD treatment. Furthermore, we propose possible future directions for the development of effective therapies targeting the crosstalk interaction points of epigenetic mechanisms involved in CMD.
Atrial septal defect (ASD) closure relieves chronic right ventricular (RV) volume overload; however, the extent to which RV mechanics and autonomic regulation normalize in the mid-term remains uncertain. Patients with isolated secundum ASD who had undergone surgical or transcatheter closure were compared with healthy controls of similar age, sex, and body surface area. Despite successful closure, ASD patients demonstrated subclinical impairment in RV systolic function and persistent enlargement of parasternal RV end-diastolic diameter (p < 0.001). Autonomic assessment revealed a higher LF/HF ratio despite preserved parasympathetic indices, indicating subtle sympathovagal imbalance. Right atrial size correlated positively with parasympathetic markers (RMSSD, pNN50) and inversely with LF/HF. Surgically treated patients exhibited lower TAPSE values and a higher prevalence of abnormal RV S′ compared with transcatheter closure. These findings suggest that ASD closure does not uniformly restore RV mechanics or autonomic balance. Larger prospective studies are needed to clarify the clinical significance of these observations.
Vascular graft remodeling and aneurysm progression are commonly studied in small animal models, but non-terminal methods for their assessment remain limited. This study evaluated contrast-enhanced micro-CT as a tool for longitudinal, in vivo monitoring of vascular grafts in rodents. Using a transplant model in which a pulmonary artery segment was implanted into the recipient’s abdominal aorta, creating a pulmonary vascular graft, we compared a molecular iodinated contrast agent with a nanoparticle-based agent. The molecular agent was rapidly cleared, resulting in insufficient vascular opacification for graft visualization or quantification. In contrast, the nanoparticle agent provided prolonged vascular enhancement, enabling high-resolution imaging and quantitative assessment of graft morphology and aneurysm development over time. These findings demonstrate that contrast-enhanced micro-CT, particularly using nanoparticulate blood-pool contrast agents, enables a longitudinal, non-terminal evaluation of vascular grafts in rodents, enabling quantitative monitoring of graft remodeling, overcoming the limitations of traditional post-mortem, single timepoint analyses.
Myocardial ischemia-reperfusion injury (MIRI) lacks fully established post-translational modification (PTM)-associated biomarkers. This study aimed to identify and validate PTM-related MIRI biomarkers through integrated bioinformatics analyses and in vitro experiments. RNA-sequencing datasets were analyzed using weighted gene co-expression network analysis (WGCNA), which identified a brown module strongly associated with the MIRI phenotype. Intersection analysis was performed among the brown gene module, differentially expressed genes, and post-translational modification-related gene sets, two core candidate genes, Myc and Rnf115, were ultimately selected. Both genes demonstrated high diagnostic potential in receiver operating characteristic analyses and exhibited positive correlations with dendritic cell and macrophage infiltration, indicating roles in immune modulation. Hypoxia/reoxygenation assays using H9C2 rat cardiomyocytes confirmed the upregulation of Myc and Rnf115 during early MIRI, aligning with bioinformatics trends. Consequently, Myc and Rnf115 were identified as promising PTM-associated biomarkers potentially involved in MIRI pathogenesis.
This study aims to investigate the therapeutic potential of NMN in alleviating type 2 diabetes-induced myocardial fibrosis.The experiment was comprised of control group, diabetic group, DM + NMN intervention group, and DM + NMN+3-TYP group. Blood glucose level, tibia length, cardiac function, myocardial interstitial fibrosis and ROS level were evaluated. The expression of SIRT3, GSK3β, ac-GSK3β, downstream fibrosis-related proteins and the interaction between SIRT3 and GSK3β were analyzed. Diabetic mice exhibited pronounced myocardial interstitial fibrosis alongside significant alterations in cardiac structure and function. Additionally, the protein expression levels of ac-GSK3β/GSK3β, p-Smad3/t-Smad3, α-SMA, and Collagen I were elevated, while SIRT3 expression was reduced. NMN effectively ameliorated these changes. The therapeutic benefits of NMN were effectively inhibited by 3-TYP. NMN effectively combats diabetes-induced myocardial fibrosis, potentially through upregulating SIRT3 expression. This upregulation may enhance the interaction between SIRT3 and GSK3β, thereby reducing the acetylation of GSK3β. Through this mechanism, NMN ultimately suppresses Smad3 phosphorylation.
Ferroptosis critically mediates myocardial ischemia/reperfusion (I/R) injury. Exercise training confers cardioprotection, but whether it protects against I/R-induced ferroptosis and the underlying mechanisms remain unclear. In this study, C57BL/6J mice underwent six weeks of treadmill exercise preconditioning (EP) before myocardial I/R induction. Cardiac function, oxidative stress, ferroptosis markers and the phosphorylation of AMPK and ACC were assessed. In vitro, H9C2 cells were subjected to hypoxia/reoxygenation (H/R), and pharmacological modulators were used to investigate the necessity of the AMPK-ACC signaling. Results showed that EP alleviated I/R-induced cardiac dysfunction, reduced oxidative stress and iron deposition, upregulated GPX4 and SLC7A11 expression, downregulated ACSL4 expression, and enhanced the phosphorylation of AMPK and ACC. In H9C2 cells, H/R reduced ACC phosphorylation and induced ferroptosis. AMPK inhibition exacerbated H/R-induced ferroptosis, whereas AMPK activation by AICAR was protective. Critically, blocking ACC enzymatic activity attenuated AICAR’s effects. These findings indicate that EP attenuates I/R-induced ferroptosis and the AMPK-ACC signaling may contribute to this protective effect.
Cardiovascular disease risk increases after menopause, largely driven by estrogen deficiency-induced endothelial dysfunction. While sodium-glucose cotransporter 2 (SGLT2) inhibitors confer cardiovascular protection, their vascular effects under estrogen-deficient conditions remain unclear. This study investigated the effects of the SGLT2 inhibitor empagliflozin on vascular function in an ovariectomized (OVX) rat model of estrogen deficiency. Female Sprague-Dawley rats were assigned to control, OVX, OVX + vehicle, OVX + empagliflozin (10 mg/kg/day), and OVX + estradiol (20 µg/kg/day) groups for 28 days. Vascular reactivity was assessed using wire myography, alongside evaluation of endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) levels. OVX rats exhibited impaired endothelium-dependent vasorelaxation, increased vasoconstriction, reduced eNOS activation, and decreased NO bioavailability. Empagliflozin significantly improved vascular reactivity, enhanced eNOS activation, and restored NO levels, with effects comparable to estradiol. These findings identify empagliflozin as a potential non-hormonal therapeutic strategy for endothelial dysfunction in postmenopausal conditions.
Obesity is a major risk factor for metabolic dysfunction and cognitive decline, yet the influence of age of onset and sex on neurovascular outcomes remains unclear. We examined how the age at initiation and duration of diet-induced obesity influence metabolism, cognition, and cerebrovascular perfusion in male and female mice. A high-fat diet increased body weight and impaired glucose regulation, particularly in females. Obesity selectively impaired recognition memory while sparing spatial working memory. Cerebrovascular effects were region- and age-specific. Early- and mid-life obesity produced localized perfusion changes despite preserved global cortical blood flow. In contrast, early-life obesity was associated with reduced cortical perfusion and decreased hippocampal vascular complexity, including fewer branch points and smaller vessel diameters. These alterations parallel recognition memory deficits, suggesting a vascular mechanism linking early metabolic stress to cognitive impairment. Together, our findings identify early-life obesity as a critical window of vulnerability for long-term neurovascular and cognitive dysfunction.
While exercise training is an established cornerstone for the prevention and treatment of cardiovascular diseases (CVDs), the underlying molecular mechanisms remain incompletely understood. Recent studies have identified long non-coding RNAs (lncRNAs) as critical epigenetic modulators that dynamically respond to physical activity and drive cardiovascular adaptation. This review provides a comprehensive overview of how exercise training reshapes lncRNA transcriptomic landscape to exert cardioprotective effects. Central to this discussion is the elucidation of lncRNA-associated competitive endogenous RNA (ceRNA) networks, which serve as pivotal regulatory axes in exercise-induced cellular responses. Additionally, we highlight the emerging significance of exercise-derived exosomal lncRNAs in mediating inter-organ communication and promoting systemic vascular health. Ultimately, this synthesis delineates current knowledge gaps and future research directions, offering a robust molecular rationale for the development and implementation of personalized exercise prescriptions in clinical cardiology.
The precise diagnosis and activity assessment of Takayasu arteritis (TA) remain challenging. Using a two-phase approach, we screened serum from 9 TA patients and 10 healthy controls via HuProt microarrays, identifying three novel autoantibodies (anti-Table 2, anti-TRAC, anti-LILRA5). These were validated by ELISA in 175 samples (61 active TA, 42 inactive TA, 72 controls). Logistic regression models were developed from training (70
Sepsis-induced cardiomyopathy (SICM) has traditionally been viewed as pump-centered contractile failure, but this paradigm fails to explain the clinical spectrum and recovery patterns. This review presents an integrative framework where immunometabolic crosstalk and organelle dysfunction drive disease, including metabolic routing defects, mitochondrial fission, ER stress, and epigenetic regulation via m6A modification and lactylation. Clinically, it proposes a four-phenotype taxonomy (hyperdynamic, hypodynamic, right ventricular-predominant, Takotsubo-like) and advocates for strain imaging and MRI over ejection fraction. Diagnostic innovation includes liquid biopsy for mitochondrial DNA, extracellular vesicles, and metabolomics. Therapeutically, metabolic resuscitation and phenotype-guided vasopressors offer disease modification. The authors call for adaptive trials, biobanking, and organelle-targeted interventions, positioning SICM as a model for precision immunometabolic medicine.
The effects of microaxial flow pump (mAFP) support on coronary flow (CF) are well characterized in failing hearts, but its impact on CF in normal hearts under different levels of left ventricular (LV) unloading remains unclear. Seven anesthetized Saanen goats underwent left thoracotomy, and an Impella 5.5 device was implanted via the left common carotid artery and operated at incremental support levels: Control (P1–2), Partial (P4–6), and Total (P7–9). Coronary perfusion pressure (CPP), coronary vascular resistance (CVR), myocardial oxygen consumption (MVO₂), and diastolic LV wall stress were calculated at each level. With increasing mAFP support, CPP increased whereas CF decreased by 32.1
Atrial fibrillation (AF) is a common arrhythmia with significant morbidity and mortality, making it essential to conduct in-depth research on its mechanisms and treatments. Animal models are important tools in AF research because they can replicate the key pathophysiological features observed in human AF. This review summarizes various small animal models of AF, focusing on the construction methods of different models, the induction techniques for AF, and the corresponding induction rates, which provide important support for studying the mechanisms of AF and evaluating pharmacological efficacy.
To examine distribution of high-sensitivity cardiac troponin I (hs-cTnI) and myoglobin in patients with suspected coronary microvascular dysfunction (CMD). This study included consecutive patients with chest pain suspected of CMD. Baseline hs-cTnI, myoglobin, and coronary flow reserve (CFR) were assessed. Patients were categorized by hs-cTnI level using the 99th percentile cutoff (28 ng/L). Multivariable regression analyses evaluated associations with impaired CFR and major adverse cardiovascular events (MACE). Among 1,524 patients, 412 (27.0
To investigate the association between cognitive function and postoperative stroke in patients undergoing off-pump coronary artery bypass grafting (CABG). We reviewed patients who underwent cognitive evaluations including Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Pittsburgh Sleep Quality Index (PSQI), and Activities of Daily Living (ADL) scale before CABG. The association between cognitive function and postoperative stroke was analyzed. A total of 1,932 patients were analyzed. Postoperatively, 34 (1.8
Existing risk stratification methods in cardiothoracic surgery do not use pre-operative bicarbonate levels. We investigate if these levels carry predictive value when compared with demographic, hematologic, and other renal function indicators. We used the MIMIC-IV database to identify 11,261 patients on the cardiothoracic surgery unit who underwent ICD-9 or ICD-10 coded cardiac procedures. 30-day mortality was then modeled with respect to these indicators. Minimum pre-operative bicarbonate level is an independent risk factor for 30-day mortality post-cardiothoracic surgery ( p=0.005 ). The lowest quartile with respect to bicarbonate had increased mortality compared to all other quartiles, suggesting that patients may be classified into high- or low-risk based on bicarbonate lesser or greater than 20 mmol/L. Minimum pre-operative bicarbonate levels carry predictive information with respect to post-operative mortality. Bicarbonate could be considered alongside existing risk stratification methods in addition to other renal function indicators to improve risk stratification.
Heart failure (HF) is closely linked to mitochondrial dysfunction, featured by abnormal energy metabolism, excessive reactive oxygen species (ROS), and imbalanced mitochondrial dynamics. Clinically, effective targeted therapies for mitochondrial dysfunction are still lacking, which aggravates HF and multi-organ injury. Mitochondrial non-coding RNAs (mt-ncRNAs) form a regulatory network critical for mitochondrial function. Among them, mitochondrial-encoded circular RNAs (mecciRNAs) and mitochondrial double-stranded RNAs (mt-dsRNAs) are research hotspots. mecciRNAs protect the heart by assisting protein import and regulating mitochondrial pores and ROS; their degradation worsens HF, while exogenous supplementation alleviates injury. mt-dsRNAs arise from aberrant mitochondrial transcription and contribute to myocardial injury and remodeling via MAVS, cGAS-STING, and PNPT1 pathways. Gene therapy targeting mecciRNAs and mt-dsRNAs combined with mitochondrial delivery represents a promising strategy for HF treatment.
