Circulating endothelial cell physiology & pathophysiology in coronary artery disease and acute coronary syndrome

<p>Summary of CEC, EPC and endothelial microparticle physiology and pathology, including mechanisms of release, and mechanisms by which cellular components contribute to local vascular thrombosis.</p> <p>Phases:<br>* Maintenance of vasculature<br>* Endothelial cell desquamation<br>* Promotion of thrombosis and hemostasis</p> <p><strong>Abstract</strong><br>Circulating endothelial cells (CEC) have been put forward as a promising biomarker for diagnosis and prognosis of coronary artery disease and acute coronary syndromes. This review entails current insights into the physiology and pathobiology of CEC, including their relationship with circulating endothelial progenitor cells and endothelial microparticles. Additionally, we present a comprehensive overview of the diagnostic and prognostic value of CEC quantification, as well as possibilities for improvement, for example by inclusion of CEC morphology, transcriptomics, and proteomics. The current stand of knowledge calls out for improved counting methods and consensus on a validated cell definition. Finally, our review accentuates the importance of large, well-designed population-based prospective studies that will have to show the clinical value of CEC as cardiovascular biomarker.</p> <p><strong> Circulating endothelial cells in coronary artery disease and acute coronary syndrome.</strong> David E. Schmidt, Marco Manca, Imo E. Hoefer. Trends in Cardiovascular Medicine (2015).</p> <p>DOI to publisher PDF http://dx.doi.org/10.1016/j.tcm.2015.01.013</p> <p>Full manuscript pre-print available from http://schmidtdav.de/research</p

BBiCat: Alpha version of a Java implementation of BBiCAT project with added License

<p>This is the Java implementation of a research project on modelling and analysis of complex systems. Release contains Local implementation of the BiMax algorithm, refactored code of BiCat toolbox, Bayesian post-analysis which uses NCI Curated Pathways database, possibilities of calling R script from Java code, Parser that maps illumina names to HGNC Symbols and usage cases of all the above mentioned. Also, a class that can read and process bigger datasets with which BiCat GUI had a trouble. Also, Mean Squared Residue Score implementation is included in the bicluster class to have a numeric metric for assessment as well.</p

DataSheet_1_Identification of a gene network driving the attenuated response to lipopolysaccharide of monocytes from hypertensive coronary artery disease patients.docx

IntroductionThe impact of cardiovascular disease (CVD) risk factors, encompassing various biological determinants and unhealthy lifestyles, on the functional dynamics of circulating monocytes—a pivotal cell type in CVD pathophysiology remains elusive. In this study, we aimed to elucidate the influence of CVD risk factors on monocyte transcriptional responses to an infectious stimulus.MethodsWe conducted a comparative analysis of monocyte gene expression profiles from the CTMM – CIRCULATING CELLS Cohort of coronary artery disease (CAD) patients, at baseline and after lipopolysaccharide (LPS) stimulation. Gene co-expression analysis was used to identify gene modules and their correlations with CVD risk factors, while pivotal transcription factors controlling the hub genes in these modules were identified by regulatory network analyses. The identified gene module was subjected to a drug repurposing screen, utilizing the LINCS L1000 database.ResultsMonocyte responsiveness to LPS showed a highly significant, negative correlation with blood pressure levels (ρ-80). We identified a ZNF12/ZBTB43-driven gene module closely linked to diastolic blood pressure, suggesting that monocyte responses to infectious stimuli, such as LPS, are attenuated in CAD patients with elevated diastolic blood pressure. This attenuation appears associated with a dampening of the LPS-induced suppression of oxidative phosphorylation. Finally, we identified the serine-threonine inhibitor MW-STK33-97 as a drug candidate capable of reversing this aberrant LPS response. ConclusionsMonocyte responses to infectious stimuli may be hampered in CAD patients with high diastolic blood pressure and this attenuated inflammatory response may be reversed by the serine-threonine inhibitor MW-STK33-97. Whether the identified gene module is a mere indicator of, or causal factor in diastolic blood pressure and the associated dampened LPS responses remains to be determined.</p