Zedoarondiol, a newly discovered compound derived from the roots of zedoary turmeric, a traditional Chinese herb, has demonstrated potential in reducing inflammation of the vascular endothelium and safeguarding it from harm. Nonetheless, the precise mechanism underlying these effects remains to be elucidated. In this study, we established a model of HUVEC injury induced by hydrogen peroxide. We observed whether Zedoarondiol could reduce the adhesion and transendothelial migration (TEM) of inflammatory cells by inhibiting the expression of VCAM-1 and ICAM-1 in HUVECs. The research findings indicate that utilising Zedoarondiol resulted in a significant reduction in the adhesion rate of THP1 cells to HUVECs, leading to a more condensed cytoskeletal structure. Moreover, Zedoarondiol demonstrated a decrease in NF-κBβ-Ser536 phosphorylation levels in H2O2-stimulated human umbilical vein endothelial cells, resulting in a hindered capacity to bind to target genes like ICAM-1 and VCAM-1, This findings may provide a new pharmacological basis and scientific evidence for Zedoarondiol to slow the atherosclerosis progression by maintaining endothelial function.
Abstract Coronary atherosclerosis is a chronic inflammatory disease that can lead to varying degrees of blood flow obstruction and a common pathophysiological basis of cardiovascular disease. Inflammatory factors run through the whole process of atherosclerotic lesions. Macrophages, T cells, and neutrophils play important roles in the process of atherosclerotic inflammation. Considering the evolutionary characteristics, atherosclerosis can be divided into different stages as early atherosclerotic plaque, plaque formation stage, and plaque rupture stage. In this paper, the changes in inflammatory cells at different stages of lesions and their related mechanisms are discussed, which can provide new insights from a clinical to bench perspective for atherosclerosis me chanism.
AbstractBackground: Left ventricular diastolic dysfunction (LVDD) caused by myocardial ischemia is an important pathogenetic factor in the development of heart failure with preserved ejection fraction (HFpEF). Objective: To explore the differences in LVDD triggered by two ischemic injuries (microvascular lesions and epicardial stenosis). Methods: Angiographic function indicators involving angiography-derived index of microcirculatory (AMR) simulating hyperemic velocity (SHV) and diagnostic indicators for LVDD including average E/e', septal e’velocity, and lateral e’velocity (based on echocardiography) were derived from records of enrolled patients suffering from coronary microvascular disease (CMVD) or obstructive coronary artery disease (CAD) (without microvascular dysfunction). The linear correlation between AMR, SHV, and echocardiographic indicators was evaluated by the Spearman's coefficient method. And logistics regression analyses evaluated risk factors for LVDD. Besides, we performed the by stratified analysis to explore Differences in AMR and SHV distribution between LVDD and non-LVDD groups. Finally, receiver operating characteristic (ROC) analyses evaluated the efficacy of AMR in recognizing LVDD. Results: CMVD was more susceptible to LVDD compared to obstructive-CAD (18.8% vs. 6.2%). AMR, SHV were linearly correlated with the relevant indicators of LVDD. And in the CMVD group, AMR were higher in the LVDD group than in the non-LVDD group, while SHV was opposite. Furthermore, AMR promoted LVDD (OR=1.02), whereas SHV inhibited the formation of LVDD (OR=0.59). ROC analyses revealed AMR can identify LADD. Conclusion: Microvascular lesions are more susceptible to LVDD.
Current treatments for coronary microvascular disease (CMVD) have limited efficacy. Kuanxiong Aerosol (KXA), a representative preparation used for aromatic and warming-up management, is a typical Chinese proprietary medicine that relieves the symptoms of angina pectoris and contributes to improving coronary microcirculation disorders, which may provide an option for the treatment of CMVD. This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 120 eligible patients will be randomized 1:1 to KXA or placebo groups and receive 30-day interventions and follow-up. The primary outcome will be the Seattle Angina Scale score. Secondary outcomes will be the TCM syndrome score, self-rating anxiety scale score and self-rating depression scale, microcirculation function, and laboratory index for coronary microvascular. This trial will evaluate the clinical efficacy and safety of KXA in the treatment of CMVD. The results of this study may provide clinical evidence for the use of Chinese patent medicine in CMVD.
Abstract Background Coronary microvascular disease (CMVD) is associated with abnormalities in glucose-lipid metabolism. And the triglyceride to high density lipoprotein (HDL) (TG/HDL) ratio can be used to characterize levels of glycolipid metabolism. Therefore, it is hypothesized that increased TG/HDL may trigger CMVD. Methods This study enrolled patients with angina pectoris but negative coronary angiograms to explore inflammatory factor-mediated disorder of glycolipid metabolism triggers CMVD. Logistics regression model and subgroup analysis were constructed to explore the associations between TG/HDL and CMVD. Restricted cubic splines were applied to further the associations of TG/HDL with CMVD. Given inflammatory factors as intermediary factor, we investigate the mediating effects of TG/HDL on CMVD. Results 242 patients were eventually recruited and 150 patients were diagnosed with CMVD. In the multivariable-adjusted model, TG/HDL and inflammatory indexes including the C-reaction protein (CRP), C-reaction protein to lymphocyte ratio (CLR) and inflammatory burden index (IBI) were positively related to CMVD (Odds Ratio (OR) = 1.71, 95% CI = 0.69–4.25; OR = 1.89, 95% CI = 1.32–2.68; OR = 2.76, 95% CI = 1.56–4.89; OR = 1.22, 95% CI = 1.08–1.37, respectively). Mediation analysis indicated that CRP, CLR and IBI mediated 26.37%, 16.89% and 10.45% of the association of TG/HDL with CMVD. Conclusion TG/HDL is positively associated with CMVD. And this association appeared to be partially mediated through inflammatory indices.
There is a lack of consensus on diagnosing coronary microvascular dysfunction (CMD) using the angiography-based index of microcirculatory resistance (Angio-IMR) due to the absence of evidence. This study aims to explore the efficacy of Angio-IMR in diagnosing CMD.
RNA methylation is associated with cardiovascular disease (CVD) occurrence and development. The purpose of this study is to visually analyze the results and research trends of global RNA methylation in CVD.Articles and reviews on RNA methylation in CVD published before 6 November 2022 were searched in the Web of Science Core Collection. Visual and statistical analysis was performed using CiteSpace 1.6.R4 advanced and VOSviewer 1.6.18.There were 847 papers from 1,188 institutions and 63 countries/regions. Over approximately 30 years, there was a gradual increase in publications and citations on RNA methylation in CVD. America and China had the highest output (284 and 259 papers, respectively). Nine of the top 20 institutions that published articles were from China, among which Fudan University represented the most. The International Journal of Molecular Sciences was the journal with the most studies. Nature was the most co-cited journal. The most influential writers were Zhang and Wang from China and Mathiyalagan from the United States. After 2015, the primary keywords were cardiac development, heart, promoter methylation, RNA methylation, and N6-methyladenosine. Nuclear RNA, m6A methylation, inhibition, and myocardial infarction were the most common burst keywords from 2020 to the present.A bibliometric analysis reveals research hotspots and trends of RNA methylation in CVD. The regulatory mechanisms of RNA methylation related to CVD and the clinical application of their results, especially m6A methylation, are likely to be the focus of future research.
Microvascular angina (MVA) is the most common cause of cardiac ischemic chest pain in patients without obstructive coronary artery disease (CAD) and lacks of effective treatment means. Medicine food homology (MFH) involves substances with both nutritional and medicinal qualities that have the potential to improve MVA symptoms as medicines, dietary supplements. However, research on MFH formula (MFHF) for MVA is not available. The study aims to generate a core MFHF for MVA through data mining and offer scientific backing for the utilization of edible medications in the prevention and alleviation of MVA. 11 databases were utilized to construct a database of MFH drugs, and the MFHF was generated through frequency analysis, association rule analysis, and clustering analysis. The composition of the formula is Codonopsis Radix, Astragali Radix, Platycodonis Radix, Persicae Semen, Glycyrrhizae Radix Et Rhizoma, Angelicae Sinensis Radix, and Allii Macrostemonis Bulbus. Through network pharmacology and molecular docking, we identified five major active components of MFHF: Adenosine, Nonanoic Acid, Lauric Acid, Caprylic Acid, and Enanthic Acid, along with nine core targets (NFKB1, ALB, AKT1, ACTB, TNF, IL6, ESR1, CASP3, and PTGS) for the improvement of MVA. These 5 active components have various biological activities, such as reducing oxidative stress, anti-inflammation, analgesia effect, inhibiting platelet aggregation, vasodilatation, vascular endothelial protection, and cardio-protection. GO and KEGG enrichment analyses revealed that MFHF mainly acted on the response to xenobiotic stimulus, integrative component of the plasma membrane, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding, pathways in cancer, lipid and atherosclerosis, human cytomegalovirus infection, and the PI3K-Akt signaling pathway, which are the main pathogenesis of MVA.
Background Poor nutritional status may affect outcomes after coronary revascularization, but the association between nutritional status and outcomes in patients undergoing coronary revascularization has not been fully evaluated. This study was based on the MIMIC-IV database to analyze the impact of baseline nutritional status on poor outcomes in patients with coronary revascularization. Methods Patients with coronary revascularization were screened from the MIMIC-IV database. A geriatric nutritional risk index (GNRI) was calculated and used to divide patients into 4 groups: no malnutrition ( Q 4: ≥96.79), mild malnutrition ( Q 3: 90.85–96.78), moderate malnutrition ( Q 2: 86.37–90.84), and severe malnutrition ( Q 1: 86.37). The primary outcome measure was 28-day mortality, and the secondary outcome measures were AKI and length of hospital stay. Cox proportional hazards model, Kaplan-Meier survival analysis, restricted cubic spline (RCS), and multiple linear regression model were used for statistical analysis, respectively, to ensure the robustness of study results. Results A total of 1,168 patients with coronary revascularization were included. The GNRI demonstrated a significant association with 28-day mortality in patients undergoing coronary revascularization. As a continuous variable, the GNRI exhibited a notable inverse correlation with mortality across unadjusted, partially adjusted, and fully adjusted Cox regression models [hazard ratios (HRs): 0.93, 0.94, 0.96, respectively; all P < 0.001]. When considered as a categorical variable, a low GNRI (first quartile, Q 1) was significantly associated with elevated mortality risks (HRs: 2.64, 2.30, 1.82 in the unadjusted, partially adjusted, and fully adjusted models, respectively; all P < 0.05). Subgroup analysis revealed a more pronounced association in patients under 65 years of age ( P for interaction = 0.014). Furthermore, reduced GNRI levels were also associated with an increased incidence of AKI and extended hospital lengths of stay. Conclusion GNRI is associated with prognosis in patients with coronary revascularization. Patients with lower GNRI had higher 28-day mortality, greater risk of AKI, and longer hospital stays.
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