The Davies lab, with interests in fundamental mechanisms of cell and tissue biomechanics, biochemistry and molecular biophysics and especially the role of hemodynamics in cardiovascular pathophysiology, has enjoyed a valuable collaborative relationship with CBIL over the past decade. The group has systematically developed in vivo / in situ molecular studies of the regulation of arterial endothelial heterogeneity in the context of hemodynamics and site-specific susceptibility to atherosclerosis (and calcific sclerosis in heart valves). In vivo differential expression of important phenotype pathways identified by high throughput methodologies are subsequently dissected under controlled conditions in tissue culture to establish regulatory mechanisms. An outline of the role of blood flow in differential endothelial phenotype expression can be found at: Davies PF. "Hemodynamic Shear Stress and the Endothelium in Cardiovascular Pathophysiology", Nature Clinical Practice Cardiovasc. Medicine (now: Nature Cardiology Reviews) 6:16-26, (2009). In this collaboration CBIL is engaged in experimental design through to analyses of high-throughput microarray and NGS data. The statistical, computational and analytical contributions of ongoing studies include microRNA and whole genome epigenetic experiments in swine and human cells.
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|Fidelity and enhanced sensitivity of differential transcription profiles following linear amplification of nanogram amounts of endothelial mRNA, Polacek et al., Physiol. Genomics, 2003||E-CBIL-3||Supplemental Material|
|Coexisting pro-inflammatory and anti-oxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta, Passerini et al., PNAS, 2004||E-CBIL-17||Supplemental Material|
|Regional determinants of arterial endothelial phenotype dominate the impact of gender or short-term exposure to a high-fat diet, Passerini et al., Biochem Biophys Res Commun., 2005||E-CBIL-41||Supplemental Material|
|Spatial heterogeneity of endothelial phenotypes correlates with side-specific vulnerability to calcification in normal porcine aortic valves, Simmons et al., Circ. Res., 2005||E-CBIL-32||Supplemental Material|
|Chronic Endoplasmic Reticulum Stress Activates Unfolded Protein Response in Arterial Endothelium in Regions of Susceptibility to Atherosclerosis, Civelek et al., Circ. Res., 2009
Coronary artery endothelial transcriptome in vivo: identification of endoplasmic reticulum stress and enhanced reactive oxygen species by gene connectivity network analysis, Civelek et al., Circ Cardiovasc Genet., 2011
|MicroRNA-10a regulation of pro-inflammatory phenotype in athero-susceptible endothelium in vivo and in vitro, Fang et al., PNAS, 2010||E-CBIL-45
Here is a list of related papers from the Davies lab.