Abstract

Overview and Specific Aims Core B will provide support for all four Projects by 1) performing vascular physiology and pharmacology experiments in the transgenic and knockout mouse models being investigated in this PPG, and 2) by coordinating the proposed studies with the Yale Mouse Metabolic Phenotyping Center (YMMC) for the detailed in vivo metabolic characterizations that are planned for several of the mouse models being studied in this Program. The proposed studies of mouse vascular physiology and metabolism being supported in this Core will provide a critical context for the data that will be generated by Program's proposed Common Experiment, which explores redox biochemistry and redox biomarkers in mouse endothelial cells. Dr. Michel, who has served as Director of the Animal Models of Arterial Dysfunction Core Lab during the current project period, is an experienced vascular biologist who has been involved in productive collaborations studying murine vascular physiology and pharmacology with the other Project Leaders. Dr. Gerald Shulman (see attached letter), a leading investigator in metabolism, is the director of the YMMC, and is already collaborating with Drs. Plutzky and Lee;Dr. Shulman will continue to consult on experimental design and analysis in the proposed studies, which are described in detail in all the individual Project descriptions above.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL048743-22
Application #
8644294
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
22
Fiscal Year
2014
Total Cost
$216,913
Indirect Cost
$95,393

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

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; 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
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
Garmaroudi, Farshid S; Handy, Diane E; Liu, Yang-Yu et al. (2016) Systems Pharmacology and Rational Polypharmacy: Nitric Oxide-Cyclic GMP Signaling Pathway as an Illustrative Example and Derivation of the General Case. PLoS Comput Biol 12:e1004822
Keating, Samuel T; Plutzky, Jorge; El-Osta, Assam (2016) Epigenetic Changes in Diabetes and Cardiovascular Risk. Circ Res 118:1706-22
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

Showing the most recent 10 out of 266 publications