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El presente argumenta y construye la curva de demanda social por la visita del lago de Zirahuén, a partir de lo que se deduce la existencia de demanda por la preservación de los recursos naturales y se propone el cambio de estrategia productiva de acuerdo a otra vocación natural y potencial del sitio que es el turismo de bajo impacto. Se obtiene el valor económico de dicho espacio recreativo, mediante el método del costo de viaje, mismo que oscila entre 26 y 29 millones de pesos. A la vez que se calcula el valor económico del sitio con base en distintos escenarios de tasa social de descuento a un período de 20 años, mismo que oscila entre 26 y 88 millones de dólares; según preferencias por conservación o aprovechamiento de los recursos. Se retoman estudios que argumentan que no sustentable la forma actual de aprovechamiento, que a la vez pone en riesgo la capacidad del sistema para ofertar el servicio ambiental recreativo para el turismo. En este sentido se fundamenta la necesidad de cambiar la estrategia de desarrollo y aprovechar una vocación productiva potencial que puede ser sustentable de la cuenca.

RNA modifications have recently gained great attention due to their extensive regulatory effects in a wide range of cellular networks and signaling pathways. In cardiovascular diseases (CVDs), several RNA changes, called "epitranscriptome" alterations, are found in all RNA molecules (tRNA, rRNA, mRNA, and ncRNAs). Unlike the epigenetic process, which influences the progression of atherosclerosis (AS), its transcriptional and post-transcriptional regulatory mechanisms are still unknown. Here, we described the main epitranscriptome signs to provide new insights into AS, including m6A, m5C, m1A, m7G, Ψ, and A-to-I editing. Moreover, we also included all current known RNA-- modifier-targeting, including small molecular inhibitors or activators, mainly designed against m6A- and m5A-related enzymes, such as METTL3, FTO, and ALKBH5. Finally, since only a few drugs, such as azacitidine and tazemetostat, targeting the DNA epigenome, have been approved by the FDA, the next challenge would be to identify molecules for targeting the RNA epitranscriptome. To date, total Panax notoginseng total saponin could reduce vascular hyperplasia via Wilms' tumor-associated protein-1 m6A-dependent. Indeed, a virtual screening allowed us to individuate a phytomolecule, the rhein, which acts as an FTO inhibitor by increasing mRNA m6A levels. In this review, we highlighted the RNA epitranscriptome pathways implicated in AS, describing their biological functions and their connections to the disease. The identification of epitranscriptome- sensitive pathways could provide novel opportunities to find predictive, diagnostic, and prognostic biomarkers for precision medicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Although mounting evidence supports that aberrant DNA methylation occurs in the hearts of patients with atrial fibrillation (AF), noninvasive epigenetic characterization of AF has not yet been defined., Methods: We investigated DNA methylome changes in peripheral blood CD4 + T cells isolated from 10 patients with AF relative to 11 healthy subjects (HS) who were enrolled in the DIANA clinical trial (NCT04371809) via reduced-representation bisulfite sequencing (RRBS)., Results: An atrial-specific PPI network revealed 18 hub differentially methylated genes (DMGs), wherein ROC curve analysis revealed reasonable diagnostic performance of DNA methylation levels found within CDK5R1 (AUC = 0.76; p = 0.049), HSPG2 (AUC = 0.77; p = 0.038), WDFY3 (AUC = 0.78; p = 0.029), USP49 (AUC = 0.76; p = 0.049), GSE1 (AUC = 0.76; p = 0.049), AIFM1 (AUC = 0.76; p = 0.041), CDK5RAP2 (AUC = 0.81; p = 0.017), COL4A1 (AUC = 0.86; p < 0.001), SEPT8 (AUC = 0.90; p < 0.001), PFDN1 (AUC = 0.90; p < 0.01) and ACOT7 (AUC = 0.78; p = 0.032). Transcriptional profiling of the hub DMGs provided a significant overexpression of PSDM6 (p = 0.004), TFRC (p = 0.01), CDK5R1 (p < 0.001), HSPG2 (p = 0.01), WDFY3 (p < 0.001), USP49 (p = 0.004) and GSE1 (p = 0.021) in AF patients vs HS., Conclusions: CDK5R1, GSE1, HSPG2 and WDFY3 resulted the best discriminatory genes both at methylation and gene expression level. Our results provide several candidate diagnostic biomarkers with the potential to advance precision medicine in AF., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background and Aims: DNA methylation is associated with gene silencing, but its clinical role in cardiovascular diseases (CVDs) remains to be elucidated. We hypothesized that extracellular vesicles (EVs) may carry epigenetic changes, showing themselves as a potentially valuable non-invasive diagnostic liquid biopsy. We isolated and characterized circulating EVs of acute coronary syndrome (ACS) patients and assessed their role on DNA methylation in epigenetic modifications., Methods: EVs were recovered from plasma of 19 ACS patients and 50 healthy subjects (HS). Flow cytometry, qRT-PCR, and Western blot (WB) were performed to evaluate both intra-vesicular and intra-cellular signals. ShinyGO, PANTHER, and STRING tools were used to perform GO and PPI network analyses., Results: ACS-derived EVs showed increased levels of DNA methyltransferases (DNMTs) (p<0.001) and Ten-eleven translocation (TET) genes reduction. Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B, were significantly increased in plasma ACS-EVs. DNA methylation analysis on PBMCs from healthy donors treated with HS- and ACS-derived EVs showed an important role of DNMTs carried by EVs. PPI network analysis evidenced that ACS-EVs induced changes in PBMC methylome. In the most enriched subnetwork, the hub gene SRC was connected to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, BAIAP2 genes that were showed to have many molecular effects on various cell types into onset of several CVDs. Modulation in gene expression after ACS-EVs treatment was confirmed for SRC, NOTCH1, FOXO3, RXRA, DGKG and BAIAP2 (p<0.05)., Conclusions: Our data showed an important role for ACS-derived EVs in gene expression modulation through de novo DNA methylation signals, and modulating signalling pathways in target cells., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease.We performed an epigenome-wide analysis of circulating CD4 + and CD8 + T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4 + T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vs HS. In CD8 + T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4 + vs T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes ( + T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes ( NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1 ) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS ( P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations ( r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 0.035, respectively).This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4 + T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology.+ T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology.

The risk of coronary heart disease (CHD) clinical manifestations and patient management is estimated according to risk scores accounting multifactorial risk factors, thus failing to cover the individual cardiovascular risk. Technological improvements in the field of medical imaging, in particular, in cardiac computed tomography angiography and cardiac magnetic resonance protocols, laid the development of radiogenomics. Radiogenomics aims to integrate a huge number of imaging features and molecular profiles to identify optimal radiomic/biomarker signatures. In addition, supervised and unsupervised artificial intelligence algorithms have the potential to combine different layers of data (imaging parameters and features, clinical variables and biomarkers) and elaborate complex and specific CHD risk models allowing more accurate diagnosis and reliable prognosis prediction. Literature from the past 5 years was systematically collected from PubMed and Scopus databases, and 60 studies were selected. We speculated the applicability of radiogenomics and artificial intelligence through the application of machine learning algorithms to identify CHD and characterize atherosclerotic lesions and myocardial abnormalities. Radiomic features extracted by cardiac computed tomography angiography and cardiac magnetic resonance showed good diagnostic accuracy for the identification of coronary plaques and myocardium structure; on the other hand, few studies exploited radiogenomics integration, thus suggesting further research efforts in this field. Cardiac computed tomography angiography resulted the most used noninvasive imaging modality for artificial intelligence applications. Several studies provided high performance for CHD diagnosis, classification, and prognostic assessment even though several efforts are still needed to validate and standardize algorithms for CHD patient routine according to good medical practice.

Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of non-Hodgkin's lymphoma. It typically has an aggressive behavior with potential clinical emergencies including cardiac tamponade, thrombosis of major neck vessels, airway obstruction, and tumor lysis syndrome. In this case report, a 38-year-old Caucasian male presented with shortness of breath, a two-month history of 40-pound weight loss, and a left-sided chest wall mass. CT imaging showed a mediastinal mass, measuring 13 × 14.6 × 8.6 cm 3 , with invasion and partial occlusion of the brachiocephalic veins and upper superior vena cava causing superior vena cava syndrome, and encasement of multiple coronary artery segments. CT-guided biopsy showed high-grade B-cell lymphoma. Cytology biomarkers were positive for CD20, CD45, and PAX5. A trans-thoracic echocardiogram (TTE) was obtained prior to chemotherapy initiation to establish a baseline for cardiac function, which showed an ejection fraction (EF) of 45-50%, right ventricle volume overload and dilation, and pulmonary hypertension. R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) chemotherapy regimen was initiated and a follow-up echocardiogram after three cycles, revealed a significant improvement in EF; the patient subsequently received three additional cycles of R-EPOCH. Current regimens in the United States utilize dose-adjusted R-EPOCH and R-CHOP, but they must be used cautiously in patients with compromised cardiac function, due to the cardiotoxic side effects of the chemotherapy agent, doxorubicin. This case illustrates that anthracycline-free regimens should be considered in patients with reduced cardiac function, with this case showing the utilization of an anthracycline-free regimen (R-CEOP) for the first three cycles, followed by a transition to R-EPOCH., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Cherukuri et al.)

The early identification of pathogenic mechanisms is essential to predict the incidence and progression of cardiomyopathies and to plan appropriate preventive interventions. Noninvasive cardiac imaging such as cardiac computed tomography, cardiac magnetic resonance, and nuclear imaging plays an important role in diagnosis and management of cardiomyopathies and provides useful prognostic information. Most molecular factors exert their functions by interacting with other cellular components, thus many diseases reflect perturbations of intracellular networks. Indeed, complex diseases and traits such as cardiomyopathies are caused by perturbations of biological networks. The network medicine approach, by integrating systems biology, aims to identify pathological interacting genes and proteins, revolutionizing the way to know cardiomyopathies and shifting the understanding of their pathogenic phenomena from a reductionist to a holistic approach. In addition, artificial intelligence tools, applied to morphological and functional imaging, could allow imaging scans to be automatically analyzed to extract new parameters and features for cardiomyopathy evaluation. The aim of this review is to discuss the tools of network medicine in cardiomyopathies that could reveal new candidate genes and artificial intelligence imaging-based features with the aim to translate into clinical practice as diagnostic, prognostic, and predictive biomarkers and shed new light on the clinical setting of cardiomyopathies. The integration and elaboration of clinical habits, molecular big data, and imaging into machine learning models could provide better disease phenotyping, outcome prediction, and novel drug targets, thus opening a new scenario for the implementation of precision medicine for cardiomyopathies., (Copyright © 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Nitric oxide (NO) is a powerful mediator with biological activities such as vasodilation and prevention of vascular smooth muscle cell proliferation as well as functional regulation of cardiac cells. Thus, impaired production or reduced bioavailability of NO predisposes to the onset of different cardiovascular (CV) diseases. Alterations in the redox balance associated with excitation-contraction coupling have been identified in heart failure (HF), thus contributing to contractile abnormalities and arrhythmias. For its ability to influence cell proliferation and angiogenesis, NO may be considered a therapeutic option for the management of several CV diseases. Several clinical studies and trials investigated therapeutic NO strategies for systemic hypertension, atherosclerosis, and/or prevention of in stent restenosis, coronary heart disease (CHD), pulmonary arterial hypertension (PAH), and HF, although with mixed results in long-term treatment and effective dose administered in selected groups of patients. Tadalafil, sildenafil, and cinaguat were evaluated for the treatment of PAH, whereas vericiguat was investigated in the treatment of HF patients with reduced ejection fraction. Furthermore, supplementation with hydrogen sulfide, tetrahydrobiopterin, and nitrite/nitrate has shown beneficial effects at the vascular level.

Background: DNA methylation can play a pathogenic role in the early stages of hyperglycemia linking homeostasis imbalance and vascular damage., Material and Methods: We investigated DNA methylome by RRBS in CD04 + and CD08 + T cells from healthy subjects (HS) to pre-diabetics (Pre-Diab) and type 2 diabetic (T2D) patients to identify early biomarkers of glucose impairment and vascular damage. Our cross-sectional study enrolled 14 individuals from HS state to increasing hyperglycemia (pilot study, PIRAMIDE trial, NCT03792607)., Results: Globally, differentially methylated regions (DMRs) were mostly annotated to promoter regions. Hypermethylated DMRs were greater than hypomethylated in CD04 + T cells whereas CD08 + T showed an opposite trend. Moreover, DMRs overlapping between Pre-Diab and T2D patients were mostly hypermethylated in both T cells. Interestingly, SPARC was the most hypomethylated gene in Pre-Diab and its methylation level gradually decreased in T2D patients. Besides, SPARC showed a significant positive correlation with DBP (+0.76), HDL (+0.54), Creatinine (+0.83), LVDd (+0.98), LVSD (+0.98), LAD (+0.98), LVPWd (+0.84), AODd (+0.81), HR (+0.72), Triglycerides (+0.83), LAD (+0.69) and AODd (+0.52) whereas a negative correlation with Cholesterol (-0.52) and LDL (-0.71) in T2D., Conclusion: SPARC hypomethylation in CD08 + T cells may be a useful biomarker of vascular complications in Pre-Diab with a possible role for primary prevention warranting further multicenter clinical trials to validate our findings., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors.)

Aims: Immune endothelial inflammation, underlying coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features., Methods: Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score = 0, uninjured coronaries and with no obstructive CHD (no critical stenosis, NCS) were considered as control subjects (n = 18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software., Results: For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p = 0.05) of HLA-G gene in CHD patients compared to control group; 2) the hypomethylation level of one specific fragment of 161bp (+616/+777) positively correlated with coronary Ca score, a relevant parameter of CCTA (p<0.05) between two groups evaluated and was predictive for disease severity., Conclusions: Reduced levels of circulating HLA-G molecules could derive from epigenetic marks. Epigenetics phenomena induce hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive non critical stenosis vs coronary stenosis individuals., Competing Interests: The authors have declared that no competing interests exist.

Adult adipose tissue-derived mesenchymal stem cells (ASCs) constitute a vital population of multipotent cells capable of differentiating into numerous end-organ phenotypes. However, scientific and translational endeavors to harness the regenerative potential of ASCs are currently limited by an incomplete understanding of the mechanisms that determine cell-lineage commitment and stemness. In the current study, we used reduced representation bisulfite sequencing (RRBS) analysis to identify epigenetic gene targets and cellular processes that are responsive to 5'-azacitidine (5'-AZA). We describe specific changes to DNA methylation of ASCs, uncovering pathways likely associated with the enhancement of their proliferative capacity. We identified 4,797 differentially methylated regions (FDR < 0.05) associated with 3,625 genes, of which 1,584 DMRs annotated to the promoter region. Gene set enrichment of differentially methylated promoters identified "phagocytosis," "type 2 diabetes," and "metabolic pathways" as disproportionately hypomethylated, whereas "adipocyte differentiation" was the most-enriched pathway among hyper-methylated gene promoters. Weighted coexpression network analysis of DMRs identified clusters associated with cellular proliferation and other developmental programs. Furthermore, the ELK4 binding site was disproportionately hyper-methylated within the promoters of genes associated with AKT signaling. Overall, this study offers numerous preliminary insights into the epigenetic landscape that influences the regenerative capacity of human ASCs., (Copyright © 2020 Pepin, Infante, Benincasa, Schiano, Miceli, Ceccarelli, Megiorni, Anastasiadou, Della Valle, Fatone, Faenza, Docimo, Nicoletti, Marchese, Wende and Napoli.)

Early identification of coronary atherosclerotic pathogenic mechanisms is useful for predicting the risk of coronary heart disease (CHD) and future cardiac events. Epigenome changes may clarify a significant fraction of this "missing hereditability", thus offering novel potential biomarkers for prevention and care of CHD. The rapidly growing disciplines of systems biology and network science are now poised to meet the fields of precision medicine and personalized therapy. Network medicine integrates standard clinical recording and non-invasive, advanced cardiac imaging tools with epigenetics into deep learning for in-depth CHD molecular phenotyping. This approach could potentially explore developing novel drugs from natural compounds (i.e. polyphenols, folic acid) and repurposing current drugs, such as statins and metformin. Several clinical trials have exploited epigenetic tags and epigenetic sensitive drugs both in primary and secondary prevention. Due to their stability in plasma and easiness of detection, many ongoing clinical trials are focused on the evaluation of circulating miRNAs (e.g. miR-8059 and miR-320a) in blood, in association with imaging parameters such as coronary calcifications and stenosis degree detected by coronary computed tomography angiography (CCTA), or functional parameters provided by FFR/CT and PET/CT. Although epigenetic modifications have also been prioritized through network based approaches, the whole set of molecular interactions (interactome) in CHD is still under investigation for primary prevention strategies.

Epigenetic-sensitive mechanisms may be correlated both to pathogenesis and prognosis of coronary heart disease (CHD). We prospectively investigated some plasma circulating microRNA levels in patients undergoing cardiac computed tomography for suspected CHD (n = 95). We show that let-7c-5p, miR-765, miR-483-5p, miR-31-5p, and miR-206 were upregulated in CHD patients (n = 66) versus healthy subjects HS (n = 29); moreover, let-7c-5p, miR-765, miR- 483-5p showed higher expression in obstructive CHD (n = 36) compared to no obstructive CHD patients (n = 66). Remarkably, miR-765, miR-93-5p, and miR-433-3p showed an upregulation in patients with critical coronary stenosis. Multivariate regression analysis demonstrated that miR-765, miR-31-5p, and miR-206 were independently associated with CHD while circulating levels of miR-765 (p = 0.035), miR-433-3p (p = 0.043), and miR-93-5p (p = 0.041) were significantly higher in critical stenosis patients. Receiver operating characteristic curve analysis revealed a good performance for miR-765, miR-93-5p, and miR-433-3p on predicting CHD severity. In conclusion, our study represents a combined epigenetic/imaging approach useful to support the diagnosis and prediction of CHD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although venous thromboembolism (VTE) shows a polygenic nature, the crossroad between genome and environment is not fully understood. Genetics explains only a part of VTE hereditability and not defined molecular causes are found in approximately 50% of thrombotic patients. Thus, a major understanding of molecular mechanisms may clarify the missing hereditability. Concerning epigenetics, a particular histone modification (citrullination) plays a key role in increasing the rate of venous occlusive events by inducing neutrophil apoptosis and expulsion of neutrophil extra-cellular traps (NETs), which may be useful biomarkers of active disease. Moreover, an over-expression of miR-320a/b, miR-582, miR-195, miR-424-5p, and miR-532, or a down-regulation of miR495, miR-136-5p and miR-26a may improve the accuracy of VTE diagnosis. No clinical studies have focused on DNA methylation in VTE. Nowadays, no validated epigenetics biomarkers are routinely used for diagnosis and prevention of VTE. In the era of personalized therapy, several clinical trials are investigating the putative role of statins, a class of lipid-lowering epigenetic-based drugs, as additional therapeutic agents in VTE. Furthermore, single nucleotide polymorphisms (SNPs) in CYP2C9, VKORC1, and MIR133 genes can help physicians to predict individual warfarin dose requirement. Consequently, a comprehensive understanding of the mechanisms involved in the control of blood clot development is crucial to design novel therapeutic strategies. This review summarizes the current clinical concepts both in genetic and epigenetic VTE framework. Furthermore, we discuss the contribution of the innovative network medicine paradigm into advancing our knowledge about molecular underpinnings needed to support novel VTE diagnostic and therapeutic options., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cardiac Magnetic Resonance (CMR), thanks to high spatial resolution and absence of ionizing radiation, has been widely used in myocardial infarction (MI) assessment to evaluate cardiac structure, function, perfusion and viability. Nevertheless, it suffers from limitations in tissue and assessment of myocardial pathophysiological changes subsequent to MI. In this issue, nanoparticle-based contrast agents offer the possibility to track biological processes at cellular and molecular level underlying the various phases of MI, infarct healing and tissue repair. In this paper, first we examine the conventional CMR protocol and its findings in MI patients. Next, we looked at how nanoparticles can help in the imaging of MI and give an overview of the major approaches currently explored. Based on the presentation of successful nanoparticle applications as contrast agents (CAs) in preclinical and clinical models, we discuss promises and outstanding challenges facing the field of CMR in MI, their translational potential and clinical application., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Nitric oxide (NO) represents the most powerful endogenous molecule with vasodilator action mainly produced by endothelial nitric oxide synthase (eNOS) enzyme. Polymorphisms and epigenetic-sensitive mechanisms can modulate the expression of eNOS gene, leading to the endothelial dysfunction. This review updates on the mechanistic role of NO in the regulation of platelet activation, as well as the impact of eNOS genetic and epigenetic modifications on arterial thrombosis onset., Design: A systematic search was addressed to examination of PubMed databases with the following terms: nitric oxide; arterial thrombosis; endothelial dysfunction; DNA variations; epigenetic modifications; personalized therapy; network medicine., Results: G894T, -786T/C, and 4b/4a variable number tandem repeat (VNTR), are the main classes of polymorphisms harbored in eNOS gene associated to increased arterial thrombosis risk. DNA methylation, histone/non-histone modifications, and microRNA (miRNAs) can modulate eNOS gene expression. Investigators largely focused on the role of miRNAs in modulating NO production in arterial thrombosis development. In detail, miR-195, and miR-582 are inversely correlated both to eNOS and NO levels, thus suggesting novel biomarkers., Conclusion: We are far from incorporating omics pathogenic data from bench to arterial thrombosis bedside. Network medicine is an emerging paradigm that ideally overcomes the current shortcomings of the reductionist approach. Despite several clinical limitations, the network-based analysis of the interactome might reveal the key nodes underlying the perturbations of the arterial thrombosis, thus advancing personalized therapy.

Circulating biomarkers available in clinical practice do not allow to stratify patients with coronary heart disease (CHD) prior the onset of a clinically relevant event. We evaluated the methylation status of specific genomic segments and gene expression in peripheral blood of patients undergoing Cardiac Computed Tomography (CCT) for CHD (n = 95). We choose to investigate cholesterol metabolism. Methylation and gene expression of low density lipoprotein receptor (LDLR), sterol regulatory element-binding factor 2 (SREBF2) and ATP-binding cassette transporter 1 (ABCA1) were evaluated by qRT-PCR. Calcium score (CACS), stenosis degree, total plaque volume (TPV), calcified plaque volume (CPV), non-calcified plaque volume (NCPV) and plaque burden (PB) were assessed in all CHD patients (n = 65). The percentage of methylation at the specific analyzed segment of LDLR promoter was higher in CHD patients vs healthy subjects (HS) (n = 30) (p = 0.001). LDLR, SREBF2 and ABCA1 mRNAs were up-regulated in CHD patients vs HS (p = 0.02; p = 0.019; p = 0.008). SREBF2 was overexpressed in patients with coronary stenosis ≥50% vs subjects with stenosis <50% (p = 0.036). After adjustment for risk factors and clinical features, ABCA1 (p = 0.005) and SREBF2 (p = 0.010) gene expression were identified as independent predictors of CHD and severity. ROC curve analysis revealed a good performance of ABCA1 on predicting CHD (AUC = 0.768; p<0.001) and of SREBF2 for the prediction of disease severity (AUC = 0.815; p<0.001). Moreover, adjusted multivariate analysis demonstrated SREBF2 as independent predictor of CPV, NCPV and TPV (p = 0.022; p = 0.002 and p = 0.006) and ABCA1 as independent predictor of NCPV and TPV (p = 0.002 and p = 0.013). CHD presence and characteristics are related to selected circulating transcriptional and epigenetic-sensitive biomarkers linked to cholesterol pathway. More extensive analysis of CHD phenotypes and circulating biomarkers might improve and personalize cardiovascular risk stratification in the clinical settings., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To compare image quality and radiation dose among different protocols in patients who underwent a 128-slice dual source computed tomography coronary angiography (DSCT-CTCA)., Methods: Ninety patients were retrospectively grouped according to heart rate (HR): 26 patients (group A) with stable HR ≤60 bpm were acquired using high pitch spiral mode (FLASH); 48 patients (group B) with irregular HR ≤60 bpm or stable HR between 60 and 70 bpm using step and shoot mode; and 16 patients (group C) with irregular HR >60 bpm or stable HR ≥70 bpm by retrospective electrocardiogram pulsing acquisition. Signal to noise ratio (SNR) and contrast to noise ratio (CNR) were measured for the main vascular structures. Moreover, the dose-length product and the effective dose were assessed., Results: Both SNR and CNR were higher in group A compared to group C (18.27 ± 0.32 vs 11.22 ± 0.50 and 16.75 ± 0.32 vs 10.17 ± 0.50; P = .001). The effective dose was lower in groups A and B (2.09 ± 1.27 mSv and 4.60 ± 2.78 mSv, respectively) compared to group C (9.61 ± 5.95 mSv) P < .0001., Conclusion: The correct selection of a low-dose, HR-matched CTCA scan protocol with a DSCT scanner provides substantial reduction of radiation exposure and better SNR and CNR., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.