Journal of Cardiovascular Translational Research最新文献

HFpEF is a prevalent and complex type of heart failure. The concurrent presence of conditions such as obesity, hypertension, hyperglycemia, and hyperlipidemia significantly increase the risk of developing HFpEF. Mitochondria, often referred to as the powerhouses of the cell, are crucial in maintaining cellular functions, including ATP production, intracellular Ca²⁺ regulation, reactive oxygen species generation and clearance, and the regulation of apoptosis. Exercise plays a vital role in preserving mitochondrial homeostasis, thereby protecting the cardiovascular system from acute stress, and is a fundamental component in maintaining cardiovascular health. In this study, we review the mitochondrial dysfunction underlying the development and progression of HFpEF. Given the pivotal role of exercise in modulating cardiovascular diseases, we particularly focus on exercise as a potential therapeutic strategy for improving mitochondrial function. Graphical abstract Note: This picture was created with BioRender.com.

Phosphatidylinositol-3 kinases (PI3Ks) play a critical role in maintaining cardiovascular health and the development of cardiovascular diseases (CVDs). Specifically, vacuolar Protein Sorting 34 (VPS34) or PIK3C3, the only member of Class III PI3K, plays an important role in CVD progression. The main function of VPS34 is inducing the production of phosphatidylinositol 3-phosphate, which, together with other essential structural and regulatory proteins in forming VPS34 complexes, further regulates the mammalian target of rapamycin activation, autophagy, and endocytosis. VPS34 is found to have crucial functions in the cardiovascular system, including dictating the proliferation and survival of vascular smooth muscle cells and cardiomyocytes and the formation of thrombosis. This review aims to summarize our current knowledge and recent advances in understanding the function and regulation of VPS34 in cardiovascular health and disease. We also discuss the current development of VPS34 inhibitors and their potential to treat CVDs.

CHI3L1 is strongly associated with atherosclerosis, but its role in macrophages remains unknown. In this study, we observed a significant up-regulation of CHI3L1 in both carotid plaques and serum of symptomatic patients, and demonstrated that CHI3L1 impairs the efferocytosis of macrophages by down-regulating crucial efferocytic mediator MFGE8 through inhibiting ATF2, which binds directly to the enhancer of MFGE8. In human plaques, we observed a negative correlation between CHI3L1 expression and both ATF2 and MFGE8 levels, further proved their involvement in plaque destabilization. Using Ldlr-/- mice with tandem carotid stenosis surgery, we demonstrated that administration of CHI3L1 protein resulted in enlarged atherosclerotic necrotic cores and decreased MFGE8 and ATF2 levels. Conversely, treatment with a CHI3L1 blocking antibody exhibited the opposite trend.In conclusion, CHI3L1 destabilizes atherosclerotic plaque by impairing macrophagic efferocytosis through the down-regulation of ATF2-induced MFGE8 expression. Targeting CHI3L1 may offer a promising therapeutic strategy for the treatment of atherosclerosis.

Severe sepsis can promote myocardial injury and cardiac dysfunction, but role of p16 in sepsis-induced myocardial injury remains undefined. PBMCs were collected from patients. Expression of inflammatory factors and NLRP3 pathway were detected by Western blotting and qPCR in WT and p16KO mice. Then detect cardiomyocyte apoptosis and ROS levels in vitro. Detailed pathways and mechanisms were revealed through quantitative proteomic analysis combined with GSEA and KEGG analysis. p16 was overexpressed in PBMCs of patient. p16 knockout alleviated cardiac dysfunction in LPS-induced mice and inhibited NLRP3 inflammasome pathway in vivo and in vitro. Quantitative proteomic analysis revealed that p16 knockout contributed to the activation of the PI3K/Akt pathway in LPS-induced cardiac injury. p16 knockout promoted activation of the PI3K/Akt pathway and ameliorated NLRP3 pathway inhibition and redox imbalance thus improving cardiac function in LPS-induced cardiomyopathy mice.

CRISPR-Cas9 gene editing technology, as an innovative biomedical tool, holds significant potential in the prevention and treatment of atherosclerosis. By precisely editing key genes such as PCSK9, CRISPR-Cas9 offers the possibility of long-term regulation of low-density lipoprotein cholesterol (LDL-C), which may reduce the risk of cardiovascular diseases. Early clinical studies of gene editing therapies like VERVE-101 have yielded encouraging results, highlighting both the feasibility and potential efficacy of this technology. However, clinical applications still face challenges such as off-target effects, immunogenicity, and long-term safety. Future research should focus on enhancing the specificity and efficiency of gene editing, optimizing delivery systems, and improving personalized treatment strategies. Additionally, the establishment of ethical and legal regulatory frameworks will be critical for the safe adoption of this technology. With the continued advancement of gene editing technology, CRISPR-Cas9 may become an important tool for treating atherosclerosis and other complex diseases.

Background: Non-invasive, continuous blood pressure monitoring technologies require additional validation beyond standard cuff-based methods. This study evaluates a non-invasive, multiparametric wearable cuffless blood pressure (BP) diagnostic monitor across all hypertension classes with diverse subjects.

Methods: A prospective, multicenter study assessed Nanowear's SimpleSense-BP performance, including induced and natural BP changes, significant BP variations (Systolic BP (SBP) ≥ ± 15 mm Hg and Diastolic BP (DBP) ≥ ± 10 mm Hg), and reference input value validity over 4 weeks.

Results: 303 subjects (18-83 yrs; 50.16% Female) participated in algorithmic development and validation (Normal - 35%, Prehypertensive - 24%, Stage 1 - 24%, Stage 2 - 17%). 54 subjects were tested for induced change performance, 149 exhibited significant changes, and 91 validated reference value duration.

Conclusions: The study clinically validated a continuous, AI-based BP diagnostic monitor using non-invasive wearable data. Further testing on diverse populations and external validation are recommended. The protocol was inspired by ISO 81060-2 and IEEE 1708:2019 standards.

Recent studies emphasize the beneficial effects of exercise on diabetic cardiomyopathy (DCM), adding to the growing body of evidence that underscores the role of exercise in improving health outcomes. Despite this, a notable gap persists in the number of healthcare providers who actively prescribe exercise as a therapeutic intervention for DCM management. In addition, exercise modulates the expression of lncRNAs, which play a pivotal role in DCM progression. Further investigation into this relationship may facilitate the identification of novel biomarkers and therapeutic targets for DCM. This review consolidates recent advances in identifying lncRNAs biomarkers in DCM, summarizing the current knowledge on dysregulated lncRNAs and their molecular mechanisms. Additionally, it offers new insights into the mechanistic roles of lncRNAs, highlighting their potential as biomarkers and therapeutic targets for DCM. Overall, this review aims to inform future research and reinforce the significance of addressing diabetes-related cardiovascular diseases to potentially improve clinical outcomes.

The prognostic value of differentially expressed senescence-related genes(DESRGs) in ST-segment elevation myocardial infarction(STEMI) patients is unclear. We used GEO2R to identify DESRGs from GSE60993 and performed functional enrichment analysis. We built an optimal prognostic model with LASSO penalized Cox regression via GSE49925. We evaluated the model with survival analysis, ROC curve, decision curve analysis, nomogram, and external validation with plasma samples. We created a prognostic signature with three dysregulated DESRGs (CDC25B, FKBP5, and ECHDC3) and two clinical variables (serum creatinine, Gensini score). The signature stratified patients into low- and high-risk groups and showed strong predictive performance within two years. The external validation confirmed the survival difference between the groups. We identified three DESRGs that were differentially expressed and prognostic in STEMI patients. The model incorporating three DESRGs showed promising prediction and utility for stratifying patients and estimating survival risk in STEMI patients.

This study explored the early diagnosis and prognostic value of copeptin in non-ST-segment elevation acute coronary syndrome (NSTE-ACS). 171 patients with chest pain or myocardial ischemia symptoms were enrolled. Patients with NSTE-ACS were further divided into the non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA). All NSTE-ACS patients were followed up to record the occurrence of Major Adverse Cardiovascular Events (MACEs). Serum copeptin concentration in the NSTE-ACS group was significantly higher than that in the control group. The Area under the curve (AUC) value of copeptin in the diagnosis of NSTE-ACS was 0.798. The combined AUC value of copeptin and hypersensitive troponin I (hs-TnI) to NSTE-ACS increased to 0.930. In addition, copeptin and hs-TnI have been proven to be independent risk factors for MACEs in patients with NSTE-ACS. The use of copeptin in combination with conventional myocardial markers contributes to the early diagnosis and short-term prognosis assessment of NSTE-ACS.

Bufalin, which is isolated from toad venom, exerts positive effects on hearts under pathological circumstance. We aimed to investigate the effects and mechanisms of bufalin on myocardial I/R injury. In vivo, bufalin ameliorated myocardial I/R injury, which characteristics with better ejection function, decreased infarct size and less apoptosis. The levels of pyroptotic proteins were increased in I/R-treated macrophages and inflammatory cytokines expressed more in I/R-induced mouse, which could be attenuated by bufalin. Bufalin also reduced H/R-treated macrophage pyroptosis in vitro. Autophagic flux blockage and ROS accumulation were reduced by bufalin in impaired macrophages. Overexpression of p62 abrogated the anti-proptosis and anti-oxidative effects of bufalin. The levels of apoptosis related proteins were changed and TUNEL-positive ratio was raised in cardiomyocytes that received conditioned medium treatment with H/R-treated macrophages, while bufalin pretreatment could reduce apoptosis. These findings indicate that bufalin may attenuate myocardial I/R injury by suppressing macrophage pyroptosis via P62 pathway.