Program Director/Principal Investigator (Last, First, Middle): Burnett, John. C. Jr. PROJECT 1 Title: Natriuretic Peptide Receptor and Cardiomyocyte Biology Project Descripfion: This proposal seeks to develop a novel, cardiac specific and ulfimately translatable therapy for diastolic heart failure (DHF) based on the cardiac specific over-expression of the natriuretic pepfide receptor (guanylyl cyclase A (GCA)) via adeno-associated viral (AAV) gene delivery. We will optimize overexpression of GCA in rodent heart, demonstrate that restoration of cardiac GCA via gene delivery prevents heart failure in GCA deficient mice (mice witli systemic (GCA""""""""uit) and mice witti cardiac specific (CS- GCAnuii) ablation ofthe GCA gene) and reverses heart failure in wild type mice with established DHF. These studies lay the foundation for translation to large mammal and human DHF in future studies. Project Leader: Margaret M. Redfield. MD;Professor of Medicine Other

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL076611-08
Application #
8495787
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
8
Fiscal Year
2013
Total Cost
$370,375
Indirect Cost
$133,781
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Kawakami, Rika; Lee, Candace Y W; Scott, Christopher et al. (2017) A human study to evaluate safety, tolerability and cyclic gmp activating properties of cenderitide in subjects with stable chronic heart failure. Clin Pharmacol Ther :
Win, Sithu; Hussain, Imad; Hebl, Virginia B et al. (2017) Inpatient Mortality Risk Scores and Postdischarge Events in Hospitalized Heart Failure Patients: A Community-Based Study. Circ Heart Fail 10:
Mohammed, Selma F; Majure, David T; Redfield, Margaret M (2016) Zooming in on the Microvasculature in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail 9:
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Wan, Siu-Hin; McKie, Paul M; Schirger, John A et al. (2016) Chronic Peptide Therapy With B-Type Natriuretic Peptide in Patients With Pre-Clinical Diastolic Dysfunction (StageĀ BĀ Heart Failure). JACC Heart Fail 4:539-547
Holditch, Sara J; Schreiber, Claire A; Burnett, John C et al. (2016) Arterial Remodeling in B-Type Natriuretic Peptide Knock-Out Females. Sci Rep 6:25623
Patel, Pratik A; Scott, Christopher G; Rodeheffer, Richard J et al. (2016) The Natural History of Patients With Isolated Metabolic Syndrome. Mayo Clin Proc 91:623-33
McKie, Paul M; Schirger, John A; Benike, Sherry L et al. (2016) Chronic subcutaneous brain natriuretic peptide therapy in asymptomatic systolic heart failure. Eur J Heart Fail 18:433-41
Sangaralingham, S Jeson; Wang, Bing H; Huang, Li et al. (2016) Cardiorenal fibrosis and dysfunction in aging: Imbalance in mediators and regulators of collagen. Peptides 76:108-14

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