scholarly journals Network Pharmacology-Based Prediction and Verification of the Targets and Mechanism for Panax Notoginseng Saponins against Coronary Heart Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Yan Dong ◽  
Lian Duan ◽  
Heng-wen Chen ◽  
Yong-mei Liu ◽  
Yun Zhang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Experimental Verification ◽  
Umbilical Vein ◽  
Bioactive Compound ◽  
Panax Notoginseng ◽  
Cardiovascular Death ◽  
Network Pharmacology ◽  
Treatment Target ◽  
Remarkable Effect

Coronary heart disease (CHD) is the worldwide leading cause for cardiovascular death. Panax notoginseng saponin (PNS), which is the main bioactive compound of panax notoginseng, has been generally accepted to exert a remarkable effect on CHD for a long time. However, to reveal the underlying treatment target and corresponding mechanism of PNS against CHD is still a substantial challenge. In this work, the targets and mechanism of PNS against CHD were successfully achieved by pharmacology-based prediction and experimental verification. 36 common targets were screened out through integrating the gene expression profile of CHD and the chemical-protein data of PNS. Then, two key nodes were further selected for verification by experiment after analyzing GO function, KEGG pathway, coexpression, and topology analysis. Results showed that PNS has protected the human umbilical vein endothelial cells from H2O2-induced oxidative stress by inhibiting early cell apoptosis via upregulating VEGFA mRNA expression. Therefore, our research has successfully pointed out one treatment target and apoptotic inhibition caused by PNS with method of integrating bioinformatics prediction and experimental verification, which has partially explained the pharmacological mechanism of PNS against CHD.

scholarly journals Fuling-Guizhi Herb Pair in Coronary Heart Disease: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Bailu Duan ◽  
Lintao Han ◽  
Shuping Ming ◽  
JingJing Li ◽  
Qiong Wang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Experimental Verification ◽  
Inflammatory Responses ◽  
Underlying Mechanism ◽  
Network Pharmacology ◽  
Myocardial Tissue ◽  
Pharmacological Mechanism ◽  
Underlying Mechanisms

The Fuling (Poria cocos)-Guizhi (Cinnamomi ramulus) herb pair (FGHP) is a commonly used traditional Chinese herbal formula with coronary heart disease (CHD) treatment potential. However, the mechanism of FGHP in the treatment of CHD was still unclear. In this study, the action targets and underlying mechanism of FGHP against CHD were successfully achieved by combined network pharmacology prediction with experimental verification. 76 common targets were screened out by overlapping the chemical-protein data of FGHP and CHD-related targets. Then, two key targets were further selected for verification by using western blot analysis after analyzing PPI, GO function, and KEGG pathway. Results indicated FGHP could alleviate CHD syndromes and regulate inflammatory responses in acute myocardial ischemia rats, and the reduction of expression of TNF-α and IL-6 in myocardial tissue would be one of its possible underlying mechanisms. Our work demonstrated that network pharmacology combined with experimental verification provides a credible method to elucidate the pharmacological mechanism of FGHP against CHD.

scholarly journals Dietary Soy Consumption and Cardiovascular Mortality among Chinese People with Type 2 Diabetes

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2513
Author(s):  
Xiaowen Wang ◽  
Jun Lv ◽  
Canqing Yu ◽  
Liming Li ◽  
Yonghua Hu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Food Consumption ◽  
Cardiovascular Mortality ◽  
International Classification Of Diseases ◽  
Cardiovascular Death ◽  
Soy Foods ◽  
Cox Proportional Hazard Regression

Randomized controlled trials showed that soy intervention significantly improved blood lipids in people with diabetes. We sought to prospectively examine the association of soy consumption with the risk of cardiovascular death among individuals with diabetes. A total of 26,139 participants with a history of diabetes were selected from the Chinese Kadoorie Biobank study. Soy food consumption was assessed by a food frequency questionnaire. Causes of death were coded by the 10th International Classification of Diseases. The Cox proportional hazard regression was used to compute the hazard ratios. During a median follow-up of 7.8 years, a total of 1626 deaths from cardiovascular disease (CVD) were recorded. Compared with individuals who never consumed soy foods, the multivariable-adjusted risks (95% confidence intervals) of CVD mortality were 0.92 (0.78, 1.09), 0.89 (0.75, 1.05), and 0.77 (0.62, 0.96) for those who consumed soy foods monthly, 1–3 days/week, and ≥4 days/week, respectively. For cause-specific cardiovascular mortality, significant inverse associations were observed for coronary heart disease and acute myocardial infarction. Higher soy food consumption was associated with a lower risk of cardiovascular death, especially death from coronary heart disease and acute myocardial infarction, in Chinese adults with diabetes.

scholarly journals A Network Pharmacology Analysis to Reveal the Molecular Mechanism of Zhizi-Danshen on Coronary Heart Disease

2020 ◽  
Author(s):  
Yue-hong Shen ◽  
Shu-lin Wang ◽  
Na Wu ◽  
Yu-chen Dai ◽  
Qian Zhou ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Endothelial Function ◽  
Signaling Pathway ◽  
Target Genes ◽  
Cardiac Fibrosis ◽  
Fluid Shear Stress ◽  
Network Pharmacology ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function

Abstract ObjectiveOur study aimed to investigate the potential mechanisms of the herb pair Zhizi-Danshen (ZD) for coronary heart disease (CHD) using network pharmacological data mining technology.MethodsThe Traditional Chinese Medicine System Pharmacology (TCMSP) database was used to collect the active ingredients of ZD and predict ZD-related target proteins. Afterwards, we identified CHD-related targets from DisGeNET database, NCBI gene database, and TTD database. The common targets both from ZD and CHD were screened by Venny2.1, which were then imported into the String database for protein-protein interaction (PPI) analysis. Finally, the GO and KEGG enrichment analysis were performed by R software, and the network construction was established using Cytoscape3.7.2.ResultsWe obtained 199 possible targets from 62 candidate ingredients of ZD and 1033 CHD-ralated targets, with 83 overlapping common target genes. Then, 11 core targets were acquired from PPI network analysis. Further, GO analysis showed that these common targets mainly influenced receptor ligand activity，cytokine activity，cytokine receptor binding，steroid hormone receptor activity, and peptide binding. KEGG pathway analysis indicated that ZD affected CHD through seven important pathways linked to vascular endothelial function regulation (fluid shear stress and atherosclerosis，AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway), imflammatory effects (IL-17 signaling pathway, TNF signaling pathway，Toll-like receptor signaling pathway)，and hormone regulation (relaxin signaling pathway). ConclusionsThis study revealed the potential pharmacological mechanisms of ZD against CHD, which were mainly associated with regulation of vascular endothelial function and inflammatory effects, promotion of vasodilatation, and prevention of cardiac fibrosis. Moreover, it provided a novel conception for the development of alternative therapies on CHD.

scholarly journals Investigation of the Adherence to Prescribed Treatment of the Patients with Coronary Heart Disease

2021 ◽  
Vol 6 (5) ◽  
pp. 263-269
Author(s):  
V. O. Shuper ◽  
◽  
S. V. Shuper ◽  
I. V. Trefanenko ◽  
G. I. Shumko ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Secondary Prevention ◽  
Cardiovascular Mortality ◽  
Healthcare Professionals ◽  
Complete Information ◽  
Cardiovascular Death ◽  
Medical Risk ◽  
Medical Risk Factors

The purpose of the study was to investigate the adherence to secondary prevention medications among patients with coronary heart disease and identify factors associated with it. Materials and methods. We examined 40 patients diagnosed with coronary heart disease of more than 50 years old, who were prescribed with optimal medication for 1 year during hospitalization. Patients` adherence was defined according to MMS-8 Morisky values for secondary prevention medications prescribed by doctors. Also, questionnaires about individual reasons of non-compliance and for individual patient`s opinion about importance and usefulness of knowledge according to risk factors of the increase of cardiovascular mortality were designed and proposed to the patients. Simple descriptive statistics were used to elucidate the characteristics of the patient population and results from individual adherence tools. Final score was analyzed and correlation between patients’ data and level of adherence to prescribed treatment were identified. A correlation matrix (using Spearman’s coefficient) was reviewed for any evidence of collinearity. Results and discussion. Our study demonstrated higher level of non-adherence with secondary prevention medications in patients with coronary heart disease (60.0%). This fact can be explained by the socioeconomic reasons, less informative strategies from the medical staff to the patients. Severe regress of adherence was demonstrated after discharge from the hospital due to subjective improvement of the patients` condition with absence of supervision by out-patient specialists. Demographic characteristics of the patients suggested that some non-modified factors can affect compliance with the prescribed treatment. Better adherence was demonstrated by female married patients with higher educational level, with family history about cardiovascular death. Also, too much prescribed medications with difficult regime of usage with non-adequate out-patient supervision may significantly decrease adherence causing development of complications which may lead to re-hospitalizations and cardiovascular death. Our investigation demonstrated also non-complete information of the patients about lifestyle and medical risk factors of the cardiovascular mortality increase. Conclusion. The results of our study can provide useful practical information on the prevalence and severity of non-adherence among patients with coronary heart disease. Analysis of the factors influencing the adherence demonstrated the main reasons from patients and healthcare professionals affecting the level of compliance with the prescribed treatment. The step towards improving adherence can be initiated by the healthcare professional to overcome the patient's concerns about the prescribed medication. It is important to continue personal monitoring of patients by healthcare professionals in the form of regular inspections of intentional and unintentional non-adherence, including factors and reasons that may change and lead to such behavior

P5529Vascular endothelial growth factor-D and mortality in suspected or known coronary heart disease patients with diabetes: a subanalysis of the ANOX study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Wada ◽  
M Suzuki ◽  
M Matsuda ◽  
Y Ajiro ◽  
T Shinozaki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Growth Factor ◽  
Coronary Angiography ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Angiogenic Growth Factors ◽  
Patients With Diabetes ◽  
Endothelial Growth Factor

Abstract Background Diabetes is a risk factor for coronary heart disease (CHD), but further risk stratification in patients with diabetes is necessary to improve the prediction and prevention of cardiovascular events and deaths. Vascular endothelial growth factor-D (VEGF-D) is a secreted glycoprotein that can act as lymphangiogenic and angiogenic growth factors through binding to its specific receptors, VEGFR-3 (Flt-4) and VEGFR-2 (KDR/Flk-1). VEGF-D signaling via VEGFR-3 plays an important role in lipoprotein metabolisms which may contribute to CHD. VEGF-D signaling has been used as a therapeutic target of human diseases such as lymphangioleiomyomatosis and refractory angina. Furthermore, in clinical settings, the VEGF-D level is already established as a diagnostic biomarker for lymphangioleiomyomatosis. However, the prognostic value of VEGF-D in suspected or known CHD patients with diabetes is unknown. Methods Serum VEGF-D levels were measured in 1,087 suspected or known CHD patients with diabetes undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict cardiovascular events (ANOX) study, and followed up for 3 years. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 147 patients died from any cause, 47 died from cardiovascular disease, and 94 developed MACE. After adjustment for established risk factors, VEGF-D levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.34; 95% confidence interval [CI], 1.21–1.47), cardiovascular death (HR, 1.40; 95% CI, 1.18–1.62), and MACE (HR, 1.22; 95% CI, 1.07–1.40). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF-D levels further improved the prediction of all-cause death (continuous net reclassification improvement [NRI], 0.258; 95% CI, 0.088–0.429; P=0.003; integrated discrimination improvement [IDI], 0.013; 95% CI, 0.002–0.024; P=0.022), but not that of cardiovascular death (NRI, 0.046; 95% CI, −0.245–0.336; P=0.759; IDI, 0.013; 95% CI, −0.005–0.031; P=0.146) or MACE (NRI, 0.064; 95% CI, −0.146–0.274; P=0.552; IDI, 0.001; 95% CI, −0.002–0.004; P=0.557). Conclusions In suspected or known CHD patients with diabetes undergoing elective coronary angiography, elevated VEGF-D levels may predict all-cause mortality independent of established risk factors and cardiovascular biomarkers. Acknowledgement/Funding The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization

scholarly journals A network pharmacology approach to reveal the protective mechanism of Salvia miltiorrhiza-Dalbergia odorifera coupled-herbs on coronary heart disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Fei Li ◽  
Jialin Duan ◽  
Meina Zhao ◽  
Shaojie Huang ◽  
Fei Mu ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Lipid Metabolism ◽  
Endothelial Function ◽  
Salvia Miltiorrhiza ◽  
Network Pharmacology ◽  
Vascular Endothelial ◽  
Bioactive Components ◽  
Vascular Endothelial Function ◽  
Dalbergia Odorifera

AbstractSalvia miltiorrhiza-Dalbergia odorifera coupled-herbs (SMDOCH) has been used to treat coronary heart disease (CHD) for thousands of years, but its unclear bioactive components and mechanisms greatly limit its clinical application. In this study, for the first time, we used network pharmacology to elucidate the mechanisms of action of SMDOCH on CHD. We collected 270 SMDOCH-related targets from 74 bioactive components and 375 CHD-related targets, with 58 overlapping common targets. Next, we performed enrichment analysis for common-target network and protein-protein interaction (PPI) network. The results showed that SMDOCH affected CHD mainly through 10 significant signaling pathways in three biological processes: ‘vascular endothelial function regulation’, ‘inflammatory response’, and ‘lipid metabolism’. Six pathways belonged to the ‘vascular endothelial function regulation’ model, which primarily regulated hormone (renin, angiotensin, oestrogen) activity, and included three key upstream pathways that influence vascular endothelial function, namely KEGG:04933, KEGG:05418, and KEGG:04066. Three pathways, namely KEGG:04668, KEGG:04064, and KEGG:04620, belonged to the ‘inflammatory response’ model. One pathway (KEGG:04920) belonged to the ‘lipid metabolism’ model. To some extent, this study revealed the potential bioactive components and pharmacological mechanisms of SMDOCH on CHD, and provided a new direction for the development of new drugs for the treatment of CHD.

scholarly journals Endotypes of primary osteoarthritis identified by plasma metabolomics analysis

Rheumatology ◽  
2020 ◽  
Author(s):  
Salem Werdyani ◽  
Ming Liu ◽  
Hongwei Zhang ◽  
Guang Sun ◽  
Andrew Furey ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Muscle Weakness ◽  
Common Factor ◽  
Bioactive Compound ◽  
Control Analysis ◽  
Metabolomics Data ◽  
Knee Oa ◽  
Cluster A ◽  
Metabolomics Analysis

Abstract Objective To identify endotypes of osteoarthritis (OA) by a metabolomics analysis. Methods Study participants included hip/knee OA patients and controls. Fasting plasma samples were metabolomically profiled. Common factor analysis and K-means clustering were applied to the metabolomics data to identify the endotypes of OA patients. Logistic regression was utilized to identify the most significant metabolites contributing to the endotypes. Clinical and epidemiological factors were examined in relation to the identified OA endotypes. Results Six hundred and fifteen primary OA patients and 237 controls were included. Among the 186 metabolites measured, 162 passed the quality control analysis. The 615 OA patients were classified in three clusters (A, 66; B, 200; and C, 349). Patients in cluster A had a significantly higher concentration of butyrylcarnitine (C4) than other clusters and controls (all P < 0.0002). Elevated C4 is thought to be related to muscle weakness and wasting. Patients in cluster B had a significantly lower arginine concentration than other clusters and controls (all P < 7.98 × 10−11). Cluster C patients had a significantly lower concentration of lysophosphatidylcholine (with palmitic acid), which is a pro-inflammatory bioactive compound, than other clusters and controls (P < 3.79 × 10−6). Further, cluster A had a higher BMI and prevalence of diabetes than other clusters (all P ≤ 0.0009), and also a higher prevalence of coronary heart disease than cluster C (P = 0.04). Cluster B had a higher prevalence of coronary heart disease than cluster C (P = 0.003) whereas cluster C had a higher prevalence of osteoporosis (P = 0.009). Conclusion Our data suggest three possible clinically actionable endotypes in primary OA: muscle weakness, arginine deficit and low inflammatory OA.

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