Core D will provide support for histochemical and immunofluorescence microscopy of vascular and adipose tissues prepared from the various mouse preparations being generated in this Program. Morphological analyses will focus on analyzing tissue markers of vascular inflammation and redox stress using histochemical and immunofluorescence approaches, as well as serum, measurements of cytokines, lipoproteins, and fatty acids. Specific experiments planned with support from Core D are presented in the individual project descriptions. Core D also will provide centralized collection, processing, and quantitative analysis of biomarkers of oxidative stress and inflammation of tissue specimens for the individual projects. This facility will primarily use histopathological, microscopic, and biochemical approaches. The quantification and characterization of this vascular disease will build on our extensive experience in analysis of both human tissue specimens, particularly atheromata, and Murine models of atherosclerosis, aortic aneurysms, and obesity. During its 15 year life, this core of our program project has built a tissue bank of more than 800 human atherosclerotic specimens preserved for a variety of analytic techniques, and quality controlled. Retrospective quality control of specimens was routinely performed by Eugenia Shvartz under supervision of Dr. Sukhova, according to a formal manual of operations. Two to four samples per year (1994 - 1999) will be used for quality immunostaining for macrophages, SMC, and endothelial cells. Recent test revealed perfect preservation and quality of cryosections obtained from 2000 -2006. Protein extracted from tissue samples snap frozen in 2000, 2001, 2004, 2005, and 2007 showed similar yield, 5.5 -11pg/mg of dry weight independently of storage time (- 80?C). This core will also measure several plasma components integral to the experimental design of the majority of projects. Over its life, this core has supported more than one hundred of publications.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL048743-21
Application #
8449157
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
21
Fiscal Year
2013
Total Cost
$101,960
Indirect Cost
$44,839
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Steinhorn, Benjamin; Sorrentino, Andrea; Badole, Sachin et al. (2018) Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction. Nat Commun 9:4044
Brown, Jonathan D; Feldman, Zachary B; Doherty, Sean P et al. (2018) BET bromodomain proteins regulate enhancer function during adipogenesis. Proc Natl Acad Sci U S A 115:2144-2149
Samokhin, Andriy O; Stephens, Thomas; Wertheim, Bradley M et al. (2018) NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary arterial hypertension. Sci Transl Med 10:
Pang, Paul; Abbott, Molly; Abdi, Malyun et al. (2018) Pre-clinical model of severe glutathione peroxidase-3 deficiency and chronic kidney disease results in coronary artery thrombosis and depressed left ventricular function. Nephrol Dial Transplant 33:923-934
Steinhorn, Benjamin; Sartoretto, Juliano L; Sorrentino, Andrea et al. (2017) Insulin-dependent metabolic and inotropic responses in the heart are modulated by hydrogen peroxide from NADPH-oxidase isoforms NOX2 and NOX4. Free Radic Biol Med 113:16-25
Handy, Diane E; Loscalzo, Joseph (2017) Responses to reductive stress in the cardiovascular system. Free Radic Biol Med 109:114-124
Ghiassian, Susan Dina; Menche, Jörg; Chasman, Daniel I et al. (2016) Endophenotype Network Models: Common Core of Complex Diseases. Sci Rep 6:27414
Maron, Bradley A; Stephens, Thomas E; Farrell, Laurie A et al. (2016) Elevated pulmonary arterial and systemic plasma aldosterone levels associate with impaired cardiac reserve capacity during exercise in left ventricular systolic heart failure patients: A pilot study. J Heart Lung Transplant 35:342-351
Bertero, Thomas; Oldham, William M; Cottrill, Katherine A et al. (2016) Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension. J Clin Invest 126:3313-35
Wang, Rui-Sheng; Loscalzo, Joseph (2016) Illuminating drug action by network integration of disease genes: a case study of myocardial infarction. Mol Biosyst 12:1653-66

Showing the most recent 10 out of 266 publications