Role of MicroRNAs in the Pathogenesis of Coronary Artery Disease.
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ABSTRACT:
SUBMITTER: Ghafouri-Fard S
PROVIDER: S-EPMC8072222 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe present study aimed to construct a network of competitive endogenous RNAs (ceRNAs) related to the pathogenesis of coronary artery disease (CAD), to provide a novel rationale for CAD treatment.MethodsBioinformatics methods were applied to screen for differentially expressed long non-coding RNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs) from the GSE68506, GSE59421, and GSE20129 datasets of the Gene Expression Omnibus (GEO) database. The miRcode database was used to predict lncRNA-binding miRNAs. The miRTarBase, miRDB, and TargetScan databases were used to predict the target genes of these miRNAs. An mRNA-miRNA-lncRNA ceRNA network of CAD was established.ResultsBetween the CAD and normal control groups there were 264 DElncRNAs, 106 DEmiRNAs, and 1,879 DEmRNAs. We screened these differentially expressed gens (DEGs) respectively. There were 21 DElncRNAs, 13 DEmiRNAs, and 143 DEmRNAs in the ceRNA network by using Cytoscape application. The DEmRNAs were involved in the PI3K-Akt signaling pathway and the NF-κB signaling pathway. The key genes in the protein-protein interaction (PPI) network were HSP90AA1, CDKN1A, MCL1, MDM2, MAPK1, ABL1, LYN, CRK, CDK9, and FAS.ConclusionsThe ceRNA network constructed in this study identified new candidate molecules for the treatment of CAD, providing some more comprehensive and higher-quality choices for the target treatment of CAD.
| S-EPMC8421985 | biostudies-literature
Project description:To date there is no clear explanation as to how Chlamydia pneumoniae heat shock protein 60 (cHSP60) gets activated either through TLR-2/4, MAPKinase (p38/JNK/ERK), apoptotic/antiapoptotic, chemokines and inflammatory cytokines pathways leading to coronary artery disease (CAD). Hence to better understanding towards cHSP60 signaling in CAD patients, we performed experiments at RNA levels in cHSP60 positive and negative groups of CAD patients. For the determination of positivity for C. pneumoniae, Helicobacter pylori, Cytomegalovirus and Herpes Simplex Virus in atheromatous plaque multiplex Real Time PCR was performed. Monoplex Real Time PCR was also performed with 16S rRNA and HSP60 gene Chlamydia pneumoniae. Further study was performed only on cHSP60 positive (negative for H. pylori, CMV & HSV-1) and cHSP60 negative (also negative for H. pylori, CMV & HSV-1) CAD patients. 1. Patients Forty patients (28 males, 12 females) in age group (51±13 year) attending Department of Cardio Thoracic & Vascular Surgery, Safdarjung Hospital, New Delhi from September 2007 to April 2008 were enrolled in the study. These patients had manifestations of CAD and were undergoing open by-pass heart surgery. Prior written consent was obtained from each patient. The study received clearance from Ethical committee, Safdarjung hospital. Patients who had a recent acute coronary syndrome or transient ischemic attack were not included in our study. 2. Atheroma collection and handling Atheromatous tissue were collected in aseptic conditions and placed in 30 ml transport medium immediately upon resection. Three types of transport medium were used for tissue: viz. Dulbecco?s phosphate-buffered saline (PBS; Gibco Life Technologies, Paisley, Scotland) for DNA, RNA later (Ambion Inc., Woodward st. Austin, Texas, USA) for RNA and optimum cutting temperature compound (Sigma, St. Louis, MO, USA) for protein. 3. Atheroma DNA & RNA isolation and testing Total DNA was isolated for checking the positivity for C. pneumoniae from atheromatous plaques as described earlier [1]. Total RNA from the atheroma samples were isolated using RNeasy fibrous tissue mini kit (Qiagen Sciences, Maryland, USA) and the concentration was determined by a RNA dye-binding assay (Pico-Green, Molecular Probes, Eugene, OR). For cDNA synthesis, RETRO script (Ambion Inc., Woodward st. Austin, Texas, USA) was used as per manufacturer instructions. For detecting positivity for C. pneumoniae, Helicobacter pylori, Cytomegalovirus and Herpes Simplex Virus in atheromatous plaques, multiplex RT-PCR was performed [as describe in reference 1]. Monoplex RT PCR amplification primers and probes were custom designed by Applied Biosystems (Foster City, CA, USA). Briefly, sequences for the 16S rRNA and HSP60 gene of the organisms of interest were aligned and inspected for regions of conserved and variable sequences. 4. Microarray experiment Further study was performed only on cHSP60 positive (negative for H. pylori, CMV & HSV-1) and cHSP60 negative (also negative for H. pylori, CMV & HSV-1) CAD patients. cHSP60 positive samples represented the test samples and cHSP60 negative samples represented the control samples. 3 samples were analysed: samples 17 and 23 were biological replicates of test samples and also performed in duplicate as technical replicates, and sample 26 was a control sample and was also performed in duplicate as a technical replicate. Reference 1. Hem C Jha, Pragya Srivastava, Aabha Divya , Jagdish Prasad, Aruna Mittal. Prevalence of Chlamydophila pneumoniae is higher in aorta and coronary artery than in carotid artery of coronary artery disease patients. APMIS, 2009: 117 (12): 905-911.
2010-05-16 | E-GEOD-19590 | biostudies-arrayexpress
Project description:Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with still growing incidence among adults and young people worldwide. Patients with T2DM are more susceptible to developing coronary artery disease (CAD) than non-diabetic individuals. The currently used diagnostic methods do not ensure the detection of CAD at an early stage. Thus, extensive research on non-invasive, blood-based biomarkers is necessary to avoid life-threatening events. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that are stable in human body fluids and easily detectable. A number of reports have highlighted that the aberrant expression of miRNAs may impair the diversity of signaling pathways underlying the pathophysiology of atherosclerosis, which is a key player linking T2DM with CAD. The preclinical evidence suggests the atheroprotective and atherogenic influence of miRNAs on every step of T2DM-induced atherogenesis, including endothelial dysfunction, endothelial to mesenchymal transition, macrophage activation, vascular smooth muscle cells proliferation/migration, platelet hyperactivity, and calcification. Among the 122 analyzed miRNAs, 14 top miRNAs appear to be the most consistently dysregulated in T2DM and CAD, whereas 10 miRNAs are altered in T2DM, CAD, and T2DM-CAD patients. This up-to-date overview aims to discuss the role of miRNAs in the development of diabetic CAD, emphasizing their potential clinical usefulness as novel, non-invasive biomarkers and therapeutic targets for T2DM individuals with a predisposition to undergo CAD.
| S-EPMC9820734 | biostudies-literature
Project description:To date there is no clear explanation as to how Chlamydia pneumoniae heat shock protein 60 (cHSP60) gets activated either through TLR-2/4, MAPKinase (p38/JNK/ERK), apoptotic/antiapoptotic, chemokines and inflammatory cytokines pathways leading to coronary artery disease (CAD). Hence to better understanding towards cHSP60 signaling in CAD patients, we performed experiments at RNA levels in cHSP60 positive and negative groups of CAD patients. For the determination of positivity for C. pneumoniae, Helicobacter pylori, Cytomegalovirus and Herpes Simplex Virus in atheromatous plaque multiplex Real Time PCR was performed. Monoplex Real Time PCR was also performed with 16S rRNA and HSP60 gene Chlamydia pneumoniae. Further study was performed only on cHSP60 positive (negative for H. pylori, CMV & HSV-1) and cHSP60 negative (also negative for H. pylori, CMV & HSV-1) CAD patients.
2010-01-06 | GSE19590 | GEO
Project description:Background: Serine proteinase inhibitor A3 (SERPINA3) has been discovered in the pathogenesis of many human diseases, but little is known about the role of SERPINA3 in coronary artery disease (CAD). Therefore, we aim to determine its relationship with CAD and its function in the pathogenesis of atherosclerosis. Methods: In total 86 patients with CAD and 64 patients with non-CAD were compared. The plasma SERPINA3 levels were measured using ELISA. Logistic regression analysis and receiver-operating characteristic (ROC) analysis were performed to illustrate the association between plasma SERPINA3 levels and CAD. In vitro, real-time PCR (RT-PCR) and immunofluorescence staining were used to determine the expression of SERPINA3 in atherosclerotic plaques and their component cells. Then rat aortic smooth muscle cells (RASMCs) were transfected with siRNA to knock down the expression of SERPINA3 and human umbilical vein endothelial cells (HUVECs) were stimulated by SERPINA3 protein. EdU assay and scratch assay were used for assessing the capability of proliferation and migration. The cell signaling pathway was evaluated by western blot and RT-PCR. Results: Patients with CAD [104.4(54.5-259.2) μg/mL] had higher levels of plasma SERPINA3 than non-CAD [65.3(47.5-137.3) μg/mL] (P = 0.004). After being fully adjusted, both log-transformed and tertiles of plasma SERPINA3 levels were significantly associated with CAD. While its diagnostic value was relatively low since the area under the ROC curve was 0.64 (95% CI: 0.55-0.73). Secreted SERPINA3 might increase the expression of inflammatory factors in HUVECs. Vascular smooth muscle cells had the highest SERPINA3 expression among the aorta compared to endothelial cells and inflammatory cells. The knockdown of SERPINA3 in RASMCs attenuated its proliferation and migration. The phosphorylated IκBα and its downstream pathway were inhibited when SERPINA3 was knocked down. Conclusions: Elevated plasma SERPINA3 levels were associated with CAD. SERPINA3 can increase inflammatory factors expression in HUVECs. It can regulate VSMCs proliferation, migration, and releasing of inflammatory factors through the NF-κB signaling pathway. Thus, SERPINA3 played a significant role in the pathogenesis of atherosclerosis.
| S-EPMC8692672 | biostudies-literature
Project description:Background-Coronary endarterectomy (CEA) has been introduced to allow revascularization in end-stage coronary artery disease (CAD). After CEA, the injured remnants of the vessel's media could result in fast neo intimal tissue ingrowth, which require an anti-proliferation agent (antiplatelet therapy (APT). We aimed to review outcomes of patients undergoing CEA within bypass surgery who received either single-APT (SAPT) or dual-APT (DAPT). Methods-We retrospectively evaluated 353 consecutive patients undergoing CEA within isolated coronary artery bypass grafting (CABG) in the period 01/2000-07/2019. After surgery, patients received either SAPT (n = 153), or DAPT (n = 200) for six months then lifelong SAPT. Endpoints included early, late survival, and freedom from major-adverse-cardiac and cerebrovascular events (MACCE), which were defined as incidence of stroke, myocardial infarction, need for coronary intervention (PCI or CABG) or death for any cause. Results-Patients' mean age was 67 ± 9.3 years; they were predominantly male 88.1%. Both DAPT- and SAPT-groups had the same extent of CAD (mean SYNTAX-Score-II: 34.1 ± 11.6 vs. 34.4 ± 17.2, p = 0.91). Postoperatively, no difference between DAPT- and SAPT-groups was reported in the incidence of low-cardiac-output syndrome (5% vs. 9.8%, p = 0.16), revision for bleeding (5% vs. 6.5% p = 0.64), 30-day mortality (4.5% vs. 5.2%, p = 0.8) or MACCE (7.5% vs. 11.8%, p = 0.19). Imaging follow-up reported significantly higher CEA and total grafts patency (90% vs. 81.5% and 95% vs. 81%, p = 0.017) in DAPT patients. Late outcomes within 97.4 ± 67.4 months show lower incidence of overall mortality (19 vs. 51%, p < 0.001) and MACCE (24.5 vs. 58.2%, p < 0.001) in the DAPT patients when compared with SAPT patients. Conclusions-Coronary endarterectomy allows revascularization in end-stage CAD when the myocardium is still viable. The use of dual APT after CEA for at least six months seems to improve mid-to-long-term patency rates and survival, and reduced the incidence of major adverse cardiac and cerebrovascular events.
| S-EPMC10051999 | biostudies-literature
Project description:Background and aimAtypical coronary artery disease (ACAD) is characterized by atypical angina pectoris or silent myocardial ischemia. However, conventional diagnostic techniques are insufficient to identify this subtype of coronary atherosclerotic pathology, and specific and sensitive markers for diagnosing ACAD are still currently lacking. The aim of the present study is to identify a novel serum microRNA (miRNA) expression profile of ACAD patients and evaluate its clinical diagnostic value.Patients and methods127 patients who were diagnosed with ACAD and 54 age-matched controls were enrolled in this study. An initial screen of miRNA expression was performed in serum samples from 35 patients and 20 controls using TaqMan Low Density Array. A stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and validation sets to confirm the levels of the altered miRNAs in 122 patients with ACAD and 68 controls. In addition, the potential target genes of the altered miRNAs were predicted using bioinformatics methods.ResultsThe TaqMan low density array and RT-qPCR analysis identified four serum miRNAs including miR-487a, miR-502, miR-208 and miR-215 that were significantly increased, while one miRNA, miR-29b, that was significantly decreased in ACAD patients compared with normal controls (P<0.05). The area under the receiver-operating-characteristic (ROC) curve (AUC) for the combined 5 serum miRNAs were 0.850 (95% CI, 0.734-0.966, P<0.001) and 0.909 (95% CI, 0.858-0.960, P<0.001) for the training set and validation set, respectively. In addition, target gene prediction showed that these five altered miRNAs are involved in affecting various aspects of cardiac or vascular remodeling, especially in the pathway involving inflammation and fibrosis.ConclusionOur findings indicate that the five altered serum miRNAs could be novel non-invasive biomarkers for ACAD and may also represent potential therapeutic targets for atherosclerosis and myocardial ischemia.
| S-EPMC4157840 | biostudies-literature
Project description:Coronary artery disease (CAD) is one of the biggest threats to human life. Circulating microRNAs (miRNAs) have been reported to be linked to the pathogenesis of CAD, indicating the possible role in CAD diagnosis. The present study aimed to explore the expression profile of plasma miRNAs and estimate their value in diagnosis for CAD. 67 Non-CAD control subjects and 88 CAD patients were enrolled. We conducted careful evaluation by RT-PCR analysis, Spearman rank correlation coefficients analysis, Receiver Operating Characteristic (ROC) curves analysis and so on. The plasma levels of six miRNAs known to be related to CAD were measured and three of them showed obvious expression change. Circulating miR-29a-3p, miR-574-3p and miR-574-5p were all significantly increased. ROC analysis revealed the probability of the three miRNAs as biomarkers with AUCs (areas under the ROC curve) of 0.830, 0.792 and 0.789, respectively. They were significantly correlated with each other in CAD patients, suggesting the possibility of joint diagnosis. The combined AUC was 0.915, much higher than each single miRNA. Therefore, our study revealed three promising biomarkers for early diagnosis of CAD. The combination of these miRNAs may act more effectively than individual ones for CAD diagnosis.
| S-EPMC6933363 | biostudies-literature
Project description:AimsMicroRNAs (miRNAs) play important roles in the pathogenesis of cardiovascular diseases. Circulating miRNAs were recently identified as biomarkers for various physiological and pathological conditions. In this study, we aimed to identify the circulating miRNA fingerprint of vulnerable coronary artery disease (CAD) and explore its potential as a novel biomarker for this disease.Methods and resultsThe Taqman low-density miRNA array and coexpression network analyses were used to identify distinct miRNA expression profiles in the plasma of patients with typical unstable angina (UA) and angiographically documented CAD (UA group, n = 13) compared to individuals with non-cardiac chest pain (control group, n = 13). Significantly elevated expression levels of miR-106b/25 cluster, miR-17/92a cluster, miR-21/590-5p family, miR-126*, and miR-451 were observed in UA patients compared to controls. These findings were validated by real-time PCR in another 45 UA patients, 31 stable angina patients, and 37 controls. In addition, miR-106b, miR-25, miR-92a, miR-21, miR-590-5p, miR-126* and miR-451 were upregulated in microparticles (MPs) isolated from the plasma of UA patients (n = 5) compared to controls (n = 5). Using flow cytometry and immunolabeling, we further found that Annexin V(+) MPs were increased in the plasma samples of UA patients compared to controls, and the majority of the increased MPs in plasma were shown to be Annexin V(+) CD31(+) MPs. The findings suggest that Annexin V(+) CD31(+) MPs may contribute to the elevated expression of the selected miRNAs in the circulation of patients with vulnerable CAD.ConclusionThe circulating miRNA signature, consisting of the miR-106b/25 cluster, miR-17/92a cluster, miR-21/590-5p family, miR-126* and miR-451, may be used as a novel biomarker for vulnerable CAD.Trial registrationChinese Clinical Trial Register, ChiCTR-OCH-12002349.
| S-EPMC3855151 | biostudies-literature
Project description:We aimed to clarify the possible functional role of hsa_circ_0000563 in coronary artery disease. Therefore, the ChIRP-MS was conducted to explore the interaction between BTBD7_hsa_circ_0000563 and proteins on a genomic scale in human peripheral blood mononuclear cell (PBMC). This project is the raw files of the proteins bound to hsa_circ_0000563 found by ChIRP-MS in PBMC.
2023-03-11 | PXD033196 | Pride