On the nonlinear relationship between wall shear stress topology and multi-directionality in coronary atherosclerosis.

BACKGROUND AND OBJECTIVE: In this paper we investigate twelve multi-directional/topological wall shear stress (WSS) derived metrics and their relationships with the formation of coronary plaques in both computational fluid dynamics (CFD) and dynamic fluid-structure interaction (FSI) frameworks. While low WSS is one of the most established biomechanical markers associated with coronary atherosclerosis progression, alone it is limited. Multi-directional and topological WSS derived metrics have been shown to be important in atherosclerosis related mechanotransduction and near-wall transport processes. However, the relationships between these twelve WSS metrics and the influence of both FSI simulations and coronary dynamics is understudied. METHODS: We first investigate the relationships between these twelve WSS derived metrics, stenosis percentage and lesion length through a parametric, transient CFD study. Secondly, we extend the parametric study to FSI, both with and without the addition of coronary dynamics, and assess their correlations. Finally, we present the case of a patient who underwent invasive coronary angiography and optical coherence tomography imaging at two time points 18 months apart. Associations between each of the twelve WSS derived metrics in CFD, static FSI and dynamic FSI simulations were assessed against areas of positive/negative vessel remodelling, and changes in plaque morphology. RESULTS: 22-32% stenosis was the threshold beyond which adverse multi-directional/topological WSS results. Each metric produced a different relationship with changing stenoses and lesion length. Transient haemodynamics was impacted by coronary dynamics, with the topological shear variation index suppressed by up to 94%. These changes appear more critical at smaller stenosis levels, suggesting coronary dynamics could play a role in the earlier stages of atherosclerosis development. In the patient case, both dynamics and FSI vs CFD changes altered associations with measured changes in plaque morphology. An appendix of the linear fits between the various FSI- and CFD-based simulations is provided to assist in scaling CFD-based results to resemble the compliant walled characteristics of FSI more accurately. CONCLUSIONS: These results highlight the potential for coronary dynamics to alter multi-directional/topological WSS metrics which could impact associations with changes in coronary atherosclerosis over time. These results warrant further investigation in a wider range of morphological settings and longitudinal cohort studies in the future.

Correlation Analysis of CML, sRAGE, and esRAGE and the Measure of Atherosclerosis of Coronary Heart Disease.

Objective: To investigate the correlation between CML, sRAGE, and esRAGE and the measure of atherosclerosis of coronary heart disease. Methods: From June 2019 to December 2021, there were 100 patients in all suffering from coronary heart disease (CHD) selected as the observation group. On the basis of Gensini score, they were divided into mild group (Gensini score < 12 points), moderate group (12 points ≤ Gensini score ≤60 points), and severe group (Gensini score > 60). Apart from that, 50 normal people staying in our hospital for physical examination were chosen as the control group in the meantime. N in each group was detected and compared ε-Carboxymethyl lysine (CML), soluble advanced glycation end product receptor (sRAGE), and endogenous secretory advanced glycation end product receptor (esRAGE). Pearson correlation coefficient was adapted to assay the relevance between CML, sRAGE, and esRAGE, as well as the degree of atherosclerosis in CHD. Receiver operator characteristic (ROC) curve was applied to during the evaluation of the diagnosis of CML, sRAGE, and esRAGE, as well as their combined detection of severe atherosclerosis in CHD. Results: In contrast with the control group, the level of serum CML together with sRAGE in the observation group was considerably elevated, while the level of esRAGE appeared in a downward trend (P < 0.05). The level of serum CML and sRAGE was directly proportional to the measure of atherosclerosis in CHD, while the level of esRAGE was inversely proportional to the measure of atherosclerosis in CHD (P < 0.05). That is to say that serum CML and sRAGE were positive in matter of the measure of atherosclerosis in CHD, while esRAGE negatively appertains to the measure of atherosclerosis in CHD (P < 0.05). Serum CML, sRAGE, and esRAGE could effectively diagnose severe atherosclerosis in CHD, and the combined detection sensitivity (89.79%), specificity (77.16%), accuracy (86.12%), positive predictive value (86.63%), negative predictive value (88.59%), and area under ROC curve (AUC) (0.924) were higher (P < 0.05). Conclusion: CML and sRAGE, as well as esRAGE, are bound up with the degree of atherosclerosis in CHD, which is conducive to clinical diagnosis and treatment.

Protective effect of liquiritin on coronary heart disease through regulating the proliferation of human vascular smooth muscle cells via upregulation of sirtuin1.

This study aimed to explore whether liquiritin affects the development of coronary heart disease by regulating the proliferation and migration of human vascular smooth muscle cells (hVSMCs). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release detection were performed to measure the toxic effects of liquiritin on hVSMCs. An in vitro atherosclerosis model in hVSMCs was established using oxidized low-density lipoprotein (ox-LDL), and cell proliferation and apoptosis were detected using an MTT assay and flow cytometry analysis. Western blotting and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) were used to detect protein and mRNA expressions, respectively. Caspase3 activity and cell migration were measured using an activity detection kit and Transwell assay, respectively. The results indicated that liquiritin at doses <160 µM had no significant effect on cell viability and LDH release in hVSMCs. Ox-LDL significantly induced cell proliferation and migration, and inhibited hVSMCs apoptosis. Liquiritin significantly inhibited cell proliferation and migration, and enhanced cell apoptosis in ox-LDL induced hVSMCs. Sirtuin1 (SIRT1) was lowly expressed in atherosclerotic plaque tissues in coronary heart disease patients and in ox-LDL-induced hVSMCs. Liquiritin improved SIRT1 expression in ox-LDL-induced hVSMCs, whereas the improvement was inhibited by Selisistat (EX 527, an effective SIRT1 inhibitor) treatment. EX 527 reversed the effects of liquiritin on cell proliferation, migration, and apoptosis in ox-LDL-induced hVSMCs In conclusion, liquiritin plays a protective role in coronary heart disease by regulating the proliferation and migration of hVSMCs by increasing SIRT1 expression.

LncRNA UCA1, miR-26a, and miR-195 in coronary heart disease patients: Correlation with stenosis degree, cholesterol levels, inflammatory cytokines, and cell adhesion molecules.

BACKGROUND: Long noncoding RNA urothelial cancer-associated 1 (lnc-UCA1) targets microRNA-26a (miR-26a) and microRNA-195 (miR-195) to participate in coronary heart disease (CHD) progression via regulation of vascular smooth muscle cell and microvascular endothelial cell viability and mobility. Therefore, this study set out to further explore the relationship between lnc-UCA1 and miR-26a and miR-195, along with their roles in the management of patients with CHD. METHODS: One hundred and thirty-six CHD patients and 70 age-/gender-matched controls were recruited in this case-control study. Their peripheral blood mononuclear cell samples were collected for lnc-UCA1, miR-26a, and miR-195 measurement. Furthermore, serum samples from CHD patients were obtained for inflammatory cytokines and cell adhesion molecules measurement. The Gensini score was used to evaluate the stenosis severity in CHD patients. RESULTS: Lnc-UCA1 expression tend to be increased, while miR-26a and miR-195 expressions were reduced in patients with CHD compared to that of controls (all p < 0.001). In CHD patients, lnc-UCA1 was negatively correlated with miR-26a (p < 0.001) and miR-195 (p = 0.014). Besides, lnc-UCA1 was positively correlated with Gensini score (p < 0.001), total cholesterol (p = 0.019), low-density lipoprotein cholesterol (p = 0.002), and C-reactive protein (p < 0.001), while miR-26a (p < 0.001) and miR-195 (p = 0.002) were negatively correlated with Gensini score. What's more, lnc-UCA1 was positively correlated with tumor necrosis factor (TNF)-α (p = 0.004), interleukin (IL)-1ß (p = 0.041), vascular cell adhesion molecule-1 (VCAM-1) (p = 0.010), and intercellular adhesion molecule-1 (ICAM-1) (p < 0.001). While miR-26a was negatively correlated with some of the individual inflammatory cytokines and cell adhesion molecules. CONCLUSION: Lnc-UCA1, miR-26a, and miR-195 may serve as potential biomarkers for CHD management.

Cholesteryl ester transfer protein inhibitory oxoacetamido-benzamide derivatives: Glide docking, pharmacophore mapping, and synthesis

Abstract Dyslipidemia is an abnormal lipid profile associated with many common diseases, including coronary heart disease and atherosclerosis. Cholesteryl ester transfer protein (CETP) is a hydrophobic plasma glycoprotein that is responsible for the transfer of cholesteryl ester from high-density lipoprotein athero-protective particles to pro-atherogenic very low-density lipoprotein and low-density lipoprotein particles. The requirement for new CETP inhibitors, which block this process has driven our current work. Here, the synthesis as well as the ligand-based and structure-based design of seven oxoacetamido-benzamides 9a-g with CETP inhibitory activity is described. An in vitro study demonstrated that most of these compounds have appreciable CETP inhibitory activity. Compound 9g showed the highest inhibitory activity against CETP with an IC50 of 0.96 µM. Glide docking data for compounds 9a-g and torcetrapib provide evidence that they are accommodated in the CETP active site where hydrophobic interactions drive ligand/CETP complex formation. Furthermore, compounds 9a-g match the features of known CETP active inhibitors, providing a rationale for their high docking scores against the CETP binding domain. Therefore, these oxoacetamido-benzamides show potential for use as novel CETP inhibitors

The Protective Effects of miR-21-Mediated Fibroblast Growth Factor 1 in Rats with Coronary Heart Disease.

AIM: The study is to verify the protective effects of miR-21-mediated fibroblast growth factor 1 (FGF1) against myocardial ischemia in rats with coronary heart disease. MATERIALS AND METHODS: Sprague-Dawley (SD) rat models of myocardial ischemia/reperfusion (MI/R) injury were constructed, and the expression of miR-21 and FGF1 in them was interfered through ischemic postconditioning. The protective effects of miR-21-mediated FGF1 on myocardium of the model rats were analyzed, and the targeted regulatory relationship between miR-21 and FGF1 was verified through myocardial cell experiments to find the mechanism of miR-21. RESULTS: MiR-21 and FGF1 with increased expression could protect the cardiac function of model rats and improve their diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR), coronary flow (CF), bax, and bcl-2 levels, but it would also cause further increase of vascular endothelial growth factor (VEGF) and decreased infarct size (INF). In addition, intervention through both miR-21 mimics and recombinant human FGF1 could highlight the above changes. Pearson correlation analysis revealed that the expression of miR-21 was positively correlated with that of FGF1, and both miR-21 and FGF1 were significantly and linearly correlated with DBP, SBP, HR, CF, INF, bax, and bcl-2, but they were not significantly correlated with the VEGF level. The myocardial cell experiment results revealed that upregulation of miR-21 or FGF1 could alleviate apoptosis caused by hypoxia/reoxygenation of myocardial cells, and inhibition of the FGF1 expression could hinder the effect of miR-21 against apoptosis of myocardial cells. Dual luciferase reporter assay revealed that transfection of miR-21-mimics could effectively raise the fluorescence intensity of pmirGLO-FGF1-3'UTR Wt but had no significant effect on that of pmirGLO-FGF1-3'UTR Mut. CONCLUSION: MiR-21 can specifically mediate the expression of FGF1 to relieve MI/R injury, protect the cardiac function, and resist apoptosis.

Expression of lncRNA-ANRIL before and after Treatment and Its Predictive Value for Short-Term Survival in Patients with Coronary Heart Disease.

This study aimed at observing the expression of lncRNA-ANRIL (ANRIL) before and after treatment and its predictive value for short-term survival in patients with coronary heart disease (CHD). Altogether, 112 patients with CHD admitted to the hospital were enrolled as a study group (SG), which was divided into a pretreatment study group (preSG) and a posttreatment study group (postSG). Further 72 healthy people undergoing physical examinations during the same period were enrolled as a control group (CG). Peripheral blood was collected from the subjects in the three groups, to detect the expression level of serum ANRIL using quantitative reverse transcription PCR (qRT-PCR). A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of ANRIL for CHD. Kaplan-Meier survival curves were plotted to analyze 3-year survival rates in high- and low-ANRIL expression groups. Cox regression was conducted to analyze independent risk factors affecting the patients. The expression level of serum ANRIL in preSG was significantly lower than those in CG and postSG (P < 0.05). According to the ROC curve, the area under the curve (AUC) of serum ANRIL for diagnosing CHD in CG was 0.894 and the optimal cutoff value was 0.639, with the sensitivity of 86.61% and the specificity of 93.67%. According to the survival curves, the 3-year overall survival rate in the high-ANRIL expression group was significantly lower than that in the low-expression group (P < 0.05). History of smoking, high total cholesterol (TC), high triglyceride (TG), high homocysteine (Hcy), and ANRIL expression were independent prognostic factors affecting the overall survival time of the patients (P < 0.05). ANRIL is poorly expressed in the peripheral blood of patients with CHD. Its detection has good sensitivity and specificity for diagnosing the disease, and its expression may be related to the poor prognosis of the patients.

Expression of Genes and Proteins of the Sarcoplasmic Reticulum Са2+-Transport Systems in Cardiomyocytes in Concomitant Coronary Heart Disease and Type 2 Diabetes Mellitus.

We compared the expression of Са2+-ATPase (SERCA2a), calsequestrin (CASQ2), ryanodine receptors (RyR2) proteins and their genes (ATP2A2, CASQ2, and RYR2) in coronary heart disease (CHD) patients with and without comorbid type 2 diabetes mellitus. All studies were performed on the right atrial appendages resected during coronary bypass surgeries. Expression of SERCA2a and RyR2 proteins and their ATP2A2 (p=0.046) and RYR2 genes in comorbid pathology was significantly (p=0.042) higher (by 1.2 and 2 times; p=0.025). The expression of CASQ2 protein and its gene did not differ significantly between the groups (p=0.82 and p=0.066, respectively). It was concluded that the expression of SERCA2a and RyR2 proteins and their genes (but not CASQ2 and its gene) is elevated in CHD associated with type 2 diabetes mellitus. Expression of the studied proteins correlated with the expression of their genes. Increased expression of CASQ2 protein and its gene can probably prevent imbalance of the Ca2+-transporting systems in cardiomyocytes and contractile dysfunction of the myocardium, even in CHD associated with type 2 diabetes mellitus.

Modulation of Vascular Smooth Muscle Cell Multiplication, Apoptosis, and Inflammatory Damage by miR-21 in Coronary Heart Disease.

This study is aimed at exploring the role and potential molecular mechanism of microRNA-21 (miR-21) in coronary heart disease (CHD). RT-qPCR analysis was conducted to detect the expression of miR-21, Sprouty 1 (SPRY1), and connexin 43 (CX43). The protein expression of SPRY1 and CX43 was measured by western blot. ELISA was performed for measuring inflammatory factors, including intercellular adhesion molecule-1 (ICAM-1) and interleukin-1 beta (IL-1ß). The target relationship between miR-21 and SPRY1 was determined by dual-luciferase reporter assay. Cell multiplication and apoptosis were detected using CCK-8 assay and flow cytometry analysis, respectively. Our results indicated that miR-21, CX43, and the level of inflammatory cytokines including ICAM-1 and IL-1ß were upregulated, while SPRY1 was downregulated in blood samples from CHD patients compared with the controls. Besides, miR-21 directly targeted SRPY-1. miR-21 could suppress SPRY1 expression and enhance CX43 expression in VSMCs. Moreover, miR-21 accelerated cell multiplication and attenuated cell apoptosis in VSMCs. Collectively, these findings suggested that miR-21 could effectively elevate VSMC multiplication and repress apoptosis by targeting SPRY1 in CHD, providing a potential target for therapeutic strategy of CHD.

SYNTAX and Coronary Artery Calcium Score Predict Atherosclerotic Plaque Formation in the Ascending Aorta.

BACKGROUND: There is no study about the relationship between the complexity of coronary artery disease (SYNTAX SCORE; SS), and coronary artery calcium (CAC) score, accompanied with aortic calcium score (ACS) levels. The objective of this study was to investigate the relationship between the preoperative SS and CAC scores accompanying ACS in isolated CABG patients and their postoperative clinical results. METHODS: This study included 130 consecutive CABG patients. The mean age of the patients was 62.3 ± 8.62 years (range: 47-84 years). SS was measured using coronary angiography by an experienced cardiologist. We investigated the ACS accompanied with CAC scores using a multidetector computed tomography (MDCT) in the same session, preoperatively. Measurements of the CAC score and ACS were measured by an experienced radiologist, who was unaware of the study in the same session. In order to investigate aortic wall pathology in patients with positive aortic calcification, we provided aortic tissue samples prior to the proximal anastomosis of bypass grafts using No:11 scalpel. RESULTS: Overall median SS was 39 ± 7.2 (range: 15-41). CAC score was zero in 34 patients (26.1%). For the patients with a CAC score of zero, the median SS was 32 ± 9.4. There was no evidence of aortic calcification or plaque formation in 62 patients (47.6%). In these patients, the median SS was 35.6 ± 11.3. No significant difference was found when both groups were compared and for those patients with a calcific score of zero (P = .85). The median CAC score and ACS were 238 ± 122 AU (range: 0-1238 AU) and 112 ± 40 AU (range: 0-730 AU), respectively (P = .0033). For patients with a CAC score and ACS ≥400 AU, the mean SYNTAX score was ≥ 37. SS was correlated with CAC score (R:0.585; P < .0001). SYNTAX was correlated with ACS (R:0.557; P < .001). In multivariate analysis of SS (OR 1.053, 95% CI: 1.003-1.106, P = .039), gender (OR 0.189, 95% CI: 0.053-0.678, P = 0.011), age (OR 1.454, 95% CI: 1.256-1.632, P = .012), and diabetes mellitus (OR 0.341, 95% CI: 1.006-1.124, P = .014) were independent predictors for CAC score and aortic calcification. CONCLUSIONS: CAC score and ACS are strongly correlated with the complexity of coronary arteries in CABG patients. The total CAC score (≥ 400 AU) was independently associated with the degree of SS (>37). To prevent MACCE and mortality in CABG patients, we suggest the measurement of CAC score accompanied with ACS using MDCT as a non-invasive method. Highlight points: • Atherosclerotic plaque formation in aorta and coronary arteries are the main risk factors for stroke and infarction in CABG operations. •SYNTAX score value and aortic atherosclerosis levels are directly correlated. •SYNTAX score may predict the complications due to atherosclerosis during heart surgery.

Identification of Key Exosome Gene Signature in Mediating Coronary Heart Disease by Weighted Gene Correlation Network Analysis.

BACKGROUND: Coronary heart disease (CHD) is the most prevalent disease with an unelucidated pathogenetic mechanism and is mediated by complex molecular interactions of exosomes. Here, we aimed to identify differentially expressed exosome genes for the disease development and prognosis of CHD. METHOD: Six CHD samples and 32 normal samples were downloaded from the exoRbase database to identify the candidate genes in the CHD. The differentially expressed genes (DEGs) were identified. And then, weighted gene correlation network analysis (WGCNA) was used to investigate the modules in coexpressed genes between CHD samples and normal samples. DEGs and the module of the WGCNA were intersected to obtain the most relevant exosome genes. After that, the function enrichment analyses and protein-protein interaction network (PPI) were performed for the particular module using STRING and Cytoscape software. Finally, the CIBERSORT algorithm was used to analyze the immune infiltration of exosome genes between CHD samples and normal samples. RESULT: We obtain a total of 715 overlapping exosome genes located at the intersection of the DEGs and key modules. The Gene Ontology enrichment of DEGs in the blue module included inflammatory response, neutrophil degranulation, and activation of CHD. In addition, protein-protein networks were constructed, and hub genes were identified, such as LYZ, CAMP, HP, ORM1, and LTF. The immune infiltration profiles varied significantly between normal controls and CHD. Finally, we found that mast cells activated and eosinophils had a positive correlation. B cell memory had a significant negative correlation with B cell naive. Besides, neutrophils and mast cells were significantly increased in CHD patients. CONCLUSION: The underlying mechanism may be related to neutrophil degranulation and the immune response. The hub genes and the difference in immune infiltration identified in the present study may provide new insights into the diagnostic and provide candidate targets for CHD.

Exploring the best monochromatic energy level in dual energy spectral imaging for coronary stents after percutaneous coronary intervention.

In this study, the optimal monochromatic energy level in dual-energy spectral CT required for imaging coronary stents after percutaneous coronary intervention (PCI) was explored. Thirty-five consecutive patients after PCI were examined using the dual-energy spectral CT imaging mode. The original images were reconstructed at 40-140 keV (10-keV interval) monochromatic levels. The in-stent and out-stent CT values at each monochromatic level were measured to calculate the signal-to-noise ratio(SNR) and contrast-to-noise ratio (CNR) for the vessel and the CT value difference between the in-stent and out-stent lumen (dCT (in-out)), which reflects the artificial CT number increase due to the beam hardening effect caused by the stents. The subjective image quality of the stent and in-stent vessel was evaluated by two radiologists using a 5-point scale. With the increase in energy level, the CT value, SNR, CNR, and dCT (in-out) all decreased. At 80 keV, the mean CT value in-stent reached (345.24 ± 93.43) HU and dCT (in-out) started plateauing. In addition, the subjective image quality of the stents and vessels peaked at 80 keV. The 80 keV monochromatic images are optimal for imaging cardiac patients with stents after PCI, balancing the enhancement and SNR and CNR in the vessels while minimizing the beam hardening artifacts caused by the stents.

Interactions between the Gut Microbiome, Lung Conditions, and Coronary Heart Disease and How Probiotics Affect These.

The importance of a healthy microbiome cannot be overemphasized. Disturbances in its composition can lead to a variety of symptoms that can extend to other organs. Likewise, acute or chronic conditions in other organs can affect the composition and physiology of the gut microbiome. Here, we discuss interorgan communication along the gut-lung axis, as well as interactions between lung and coronary heart diseases and between cardiovascular disease and the gut microbiome. This triangle of organs, which also affects the clinical outcome of COVID-19 infections, is connected by means of numerous receptors and effectors, including immune cells and immune-modulating factors such as short chain fatty acids (SCFA) and trimethlamine-N-oxide (TMAO). The gut microbiome plays an important role in each of these, thus affecting the health of the lungs and the heart, and this interplay occurs in both directions. The gut microbiome can be influenced by the oral uptake of probiotics. With an improved understanding of the mechanisms responsible for interorgan communication, we can start to define what requirements an 'ideal' probiotic should have and its role in this triangle.

Functional versus morphological assessment of vascular age in patients with coronary heart disease.

Communicating cardiovascular risk based on individual vascular age (VA) is a well acknowledged concept in patient education and disease prevention. VA may be derived functionally, e.g. by measurement of pulse wave velocity (PWV), or morphologically, e.g. by assessment of carotid intima-media thickness (cIMT). The purpose of this study was to investigate whether both approaches produce similar results. Within the context of the German subset of the EUROASPIRE IV survey, 501 patients with coronary heart disease underwent (a) oscillometric PWV measurement at the aortic, carotid-femoral and brachial-ankle site (PWVao, PWVcf, PWVba) and derivation of the aortic augmentation index (AIao); (b) bilateral cIMT assessment by high-resolution ultrasound at three sites (common, bulb, internal). Respective VA was calculated using published equations. According to VA derived from PWV, most patients exhibited values below chronological age indicating a counterintuitive healthier-than-anticipated vascular status: for VAPWVao in 68% of patients; for VAAIao in 52% of patients. By contrast, VA derived from cIMT delivered opposite results: e.g. according to VAtotal-cIMT accelerated vascular aging in 75% of patients. To strengthen the concept of VA, further efforts are needed to better standardise the current approaches to estimate VA and, thereby, to improve comparability and clinical utility.

The Therapeutic Role of Slit2 in Anti-fibrosis, Anti-inflammation and Anti-oxidative Stress in Rats with Coronary Heart Disease.

To investigate the efficacy of Slit2 in the rats with coronary heart disease (CHD). CHD model were constructed by feeding high-fat food and injecting with pituitrin in rat, followed by recombinant Slit2 treatment, and then the cardiac function was evaluated by echocardiography, and the indicators concerning the cardiomyocyte injury markers and lipoprotein status and oxidative stress were measured. The Slit2 expression in the heart tissues was identified by immunofluorescence. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect inflammatory cytokines, H2DCFDA staining to determine the ROS generation in heart tissues, Masson trichrome staining to observe myocardial fibrosis, and qRT-PCR and Western blotting to detect gene and protein expressions. Slit2 decreased the levels of LDH, CK-MB, cTnI, TG, TC and LDL-C and increased HDL-C level in CHD rats. In the normal heart tissues, Slit2 expression was significantly lower in cardiomyocytes than cardiac fibroblasts. Furthermore, the expressions of VCAM-1, ICAM-1, fibronectin and TGF-ß1 were increased in the heart tissues of CHD rats with the obvious myocardial fibrosis, which were dose-dependently reversed by recombinant Slit2. In addition, recombinant Slit2 also dose-dependently increased the activity of NO, SOD, CAT and GSH-Px, and decreased TNF-α, IL-6, MCP-1, MDA and ROS in CHD rats. Slit2 was downregulated in myocardial tissue and plasma of CHD rats. Recombinant Slit2, by regulating the level of blood lipid, can relieve the myocardial fibrosis, inflammation and oxidative stress in CHD.

The Role of Galectin-3 and ST2 in Cardiology: A Short Review.

Galectin-3 is a lectin that binds beta-galactosides. It is involved in cardiac remodeling and fibrosis through the activation of macrophages and fibroblasts. ST2 is secreted by myocardial cells due to cardiac overload. These two biomarkers have been traditionally studied in the field of heart failure to guide medical therapy and detect the progression of the disease. Nevertheless, there are novel evidences that connect galectin-3 and ST2 with coronary heart disease and, specifically, with atrial fibrillation. The aim of this article is to concisely review the diagnostic and prognostic role of galectin-3 and ST2 in different cardiac diseases.

Association of Lipoprotein (a) variants with risk of cardiovascular disease: a Mendelian randomization study.

BACKGROUND: There is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); however, causal evidence, especially from the Chinese population, is lacking. Therefore, this study aims to estimate the causal association between variants in genes affecting Lp(a) concentrations and CVD in people of Han Chinese ethnicity. METHODS: Two-sample Mendelian randomization analysis was used to assess the causal effect of Lp(a) concentrations on the risk of CVD. Summary statistics for Lp(a) variants were obtained from 1256 individuals in the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei. Data on associations between single-nucleotide polymorphisms (SNPs) and CVD were obtained from recently published genome-wide association studies. RESULTS: Thirteen SNPs associated with Lp(a) levels in the Han Chinese population were used as instrumental variables. Genetically elevated Lp(a) was inversely associated with the risk of atrial fibrillation [odds ratio (OR), 0.94; 95% confidence interval (95%CI), 0.901-0.987; P = 0.012)], the risk of arrhythmia (OR, 0.96; 95%CI, 0.941-0.990; P = 0.005), the left ventricular mass index (OR, 0.97; 95%CI, 0.949-1.000; P = 0.048), and the left ventricular internal dimension in diastole (OR, 0.97; 95%CI, 0.950-0.997; P = 0.028) according to the inverse-variance weighted method. No significant association was observed for congestive heart failure (OR, 0.99; 95% CI, 0.950-1.038; P = 0.766), ischemic stroke (OR, 1.01; 95%CI, 0.981-1.046; P = 0.422), and left ventricular internal dimension in systole (OR, 0.98; 95%CI, 0.960-1.009; P = 0.214). CONCLUSIONS: This study provided evidence that genetically elevated Lp(a) was inversely associated with atrial fibrillation, arrhythmia, the left ventricular mass index and the left ventricular internal dimension in diastole, but not with congestive heart failure, ischemic stroke, and the left ventricular internal dimension in systole in the Han Chinese population. Further research is needed to identify the mechanism underlying these results and determine whether genetically elevated Lp(a) increases the risk of coronary heart disease or other CVD subtypes.

Long non-coding RNA THRIL is upregulated in coronary heart disease and binds to microRNA-424 to upregulate TXNIP in mice.

Cardiovascular disease, particularly coronary heart disease (CHD), is one of the diseases with the highest fatality. The close correlation between long non-coding RNAs (lncRNAs) and the occurrence and development of myocardial injury has been highlighted recently. This article mainly focused on the regulation of THRIL on myocardial injury caused by CHD in mice. After establishment of a mouse model with CHD, a lncRNA microarray analysis was performed on mouse myocardial tissues to detect differentially expressed lncRNAs, followed by RT-qPCR validation. CHD was induced in mice by high-fat diet feeding and THRIL was silenced using si-THRIL. The results showed that treating CHD mice with si-THRIL attenuated myocardial damage by restoring LVEF, LVFS, and HDL-C levels, while lowering HMI, LVMI, TC, TG, LDL-C, CK-MB, and cTnI levels. Meanwhile, mechanistical studies using bioinformatics prediction, dual-luciferase and subcellular fractionation assays revealed that THRIL bound to microRNA (miR)-424, inhibited miR-424 interaction with TXNIP and promoted TXNIP expression in the myocardial tissues. The cardioprotective effects of si-THRIL on mice were attenuated when miR-424 was downregulated. Moreover, TXNIP exerted its effects on myocardial injury by mediating the p53 pathway. Taken together, this study demonstrated that THRIL inhibition alleviates myocardial injury in CHD possibly through the miR-424/TXNIP/p53 axis.

Significances of viable synergistic autophagy-associated cathepsin B and cathepsin D (CTSB/CTSD) as potential biomarkers for sudden cardiac death.

BACKGROUND: The Cathepsins family, including cathepsin B and cathepsin D, potentially affects the entire processes involved in atherosclerosis. Although coronary heart disease (CHD) has been widely studied as the basis of Sudden Cardiac Death (SCD), the relationship between CHD and CTSB/D remains unclear. METHODS: We screened for differentially expressed proteins (DEPs) associated with autophagy by limma package in R. For the genes corresponding to the DEPs after screening, we used various databases to carry out functional enrichment of related DEGs to explore their possible influence on a specific aspect of the disease. Functional enrichment analysis of DEGs was performed by DAVID, Metascape and GSEA. STRING and Cytoscape were obtained the hub genes, the analysis of interaction networks through the GENMANIA and Networkanalyst. Western Blot was used to validate the protein expression level of target genes. TF and miRNA prediction were performed using Networkanalyst and visualized using Cytoscape. RESULTS: The expression levels of members of the cathepsin family were up regulated in CHD tissues compared with the control. GO and KEGG revealed that cathepsin was markedly enriched in endopeptidase activities, immune responses, lysosome pathways, et al. The correlation analysis showed that in patients with CHD, the CTSB/CTSD expression were negatively correlated with ATG4D and BNIP3, but positively with BCL2L1, CAPNS1, and TP53. In the TF-mRNA-miRNA network, has-miR-24-3p and has-miR-128-3p had higher degrees, CTSB/CTSD could be targeted by them. CONCLUSIONS: Our findings elucidated the expression and regulatory role of cathepsins in coronary heart disease induced SCD and might further explore the potential mechanisms of autophagy in CHD.

Allograft or Recipient ST2 Deficiency Oppositely Affected Cardiac Allograft Vasculopathy via Differentially Altering Immune Cells Infiltration.

The role of IL-33/ST2 signaling in cardiac allograft vasculopathy (CAV) is not fully addressed. Here, we investigated the role of IL-33/ST2 signaling in allograft or recipient in CAV respectively using MHC-mismatch murine chronic cardiac allograft rejection model. We found that recipients ST2 deficiency significantly exacerbated allograft vascular occlusion and fibrosis, accompanied by increased F4/80+ macrophages and CD3+ T cells infiltration in allografts. In contrast, allografts ST2 deficiency resulted in decreased infiltration of F4/80+ macrophages, CD3+ T cells and CD20+ B cells and thus alleviated vascular occlusion and fibrosis of allografts. These findings indicated that allografts or recipients ST2 deficiency oppositely affected cardiac allograft vasculopathy/fibrosis via differentially altering immune cells infiltration, which suggest that interrupting IL-33/ST2 signaling locally or systematically after heart transplantation leads different outcome.