Core B: The Immunohistochemstry (IHC) Core will provide characterization of the composition and architecture of vascular lesions (atherosclerosis, aortic aneurysms and femoral artery wire-induced injury) (Projects 1 &4), and ofthe temporal and spatial regulation of vascular gene expression by hemodynamic forces and hypercholesterolemia (Project 5) using standardized protocols. Services include (i) training personnel in individual projects to harvest and embed tissue appropriately for IHC analysis, (ii) cutting and mounting of cryostat sections in a manner that allows quantitative analysis of morphologic regions over defined areas of lesion, (iii) histochemical and immunohistochemical staining and counterstaining of serial sections, (iv) image analysis of processed tissue and training in quantitative image analysis of personnel in individual projects, (v) generation of and training in the generation of publication quality composites of images. In addition to already standardized protocols for the detection of for example, various infiltrating inflammatory cell types, foam cells, endothelial cells, vascular smooth muscle cells (at various stages of differentiation), cycling cells, apoptotic cells and extracellular matrix components, the core will develop optimized protocols for detection of additional antigens (such as PAF for platelet involvement), markers of oxidative responses and markers of the unfolded protein response as needed to support each project. The Core Director will participate up front in designing animal studies that will require IHC analysis to ensure that tissues from optimal numbers of animals per group and at optimal time points will be available for analysis, and in determining the appropriate panel of targets to be analysed to address specific hypotheses regarding mechanisms underlying lesion the development, composition and architecture of lesions. The Core Director will assist individuals from the various projects in interpreting IHC results. Core activities will utilize existing equipment including a Microm HM505 E cryostat, Leica Leitz DMRD upright microscope with bright field illumination, Nikon E 600 upright microscope with bright field illumination. Image Pro Plus image analysis software (Media Cybernetics, Silver Spring, MD), HP color laserjet 2550 LN and Canon Image Press Cl printers. Procedures for coordinated scheduling and for assuring equitable access to core services are in place. The histochemical and immunohistochemical analysis provided by the Core will provide additional approaches for quantification of the extent of lesion and will provide important insights into the mechanisms that modulate the extent of lesions as well as the properties of lesions that can impact outcome, i.e. more fibrotic versus inflammatory atherosclerotic lesions that may translate into vulnerability to plaque rupture.
Cardiovascular disease (CVD) is the number one cause of death in the United States. The technology, provided by the Immunohistochemistry Core will facilitate the research in this Program to understand the mechanisms by which genetic and environmental risk factors contribute to CVD and put patients at risk for acute events such as myocardial infarcts and strokes. This knowledge will provide a framework for the development of treatments to prevent and reverse the risk of such events.
|Tang, Soon Yew; Monslow, James; R Grant, Gregory et al. (2016) Cardiovascular Consequences of Prostanoid I Receptor Deletion in Microsomal Prostaglandin E Synthase-1-Deficient Hyperlipidemic Mice. Circulation 134:328-38|
|Jiang, Yi-Zhou; Manduchi, Elisabetta; Stoeckert Jr, Christian J et al. (2015) Arterial endothelial methylome: differential DNA methylation in athero-susceptible disturbed flow regions in vivo. BMC Genomics 16:506|
|Liu, Shu-Lin; Bae, Yong Ho; Yu, Christopher et al. (2015) Matrix metalloproteinase-12 is an essential mediator of acute and chronic arterial stiffening. Sci Rep 5:17189|
|Han, Jingyan; Shuvaev, Vladimir V; Davies, Peter F et al. (2015) Flow shear stress differentially regulates endothelial uptake of nanocarriers targeted to distinct epitopes of PECAM-1. J Control Release 210:39-47|
|Jiang, Yi-Zhou; Manduchi, Elisabetta; JimÃ©nez, Juan M et al. (2015) Endothelial epigenetics in biomechanical stress: disturbed flow-mediated epigenomic plasticity in vivo and in vitro. Arterioscler Thromb Vasc Biol 35:1317-26|
|Sweet, Daniel T; JimÃ©nez, Juan M; Chang, Jeremy et al. (2015) Lymph flow regulates collecting lymphatic vessel maturation in vivo. J Clin Invest 125:2995-3007|
|Hsu, Bernadette Y; Bae, Yong Ho; Mui, Keeley L et al. (2015) Apolipoprotein E3 Inhibits Rho to Regulate the Mechanosensitive Expression of Cox2. PLoS One 10:e0128974|
|Tang, Soon Yew; Monslow, James; Todd, Leslie et al. (2014) Cyclooxygenase-2 in endothelial and vascular smooth muscle cells restrains atherogenesis in hyperlipidemic mice. Circulation 129:1761-9|
|JimÃ©nez, Juan M; Prasad, Varesh; Yu, Michael D et al. (2014) Macro- and microscale variables regulate stent haemodynamics, fibrin deposition and thrombomodulin expression. J R Soc Interface 11:20131079|
|Jiang, Yi-Zhou; JimÃ©nez, Juan M; Ou, Kristy et al. (2014) Hemodynamic disturbed flow induces differential DNA methylation of endothelial Kruppel-Like Factor 4 promoter in vitro and in vivo. Circ Res 115:32-43|
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