Abstract

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 with systemic (GCAnull) and mice with cardiac specific (CS- GCAnull) ablation of the 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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL076611-10
Application #
8853315
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
2016-06-30
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
10
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905

  Publications

Ichiki, Tomoko; Dzhoyashvili, Nina; Burnett Jr, John C (2018) Natriuretic peptide based therapeutics for heart failure: Cenderitide: A novel first-in-class designer natriuretic peptide. Int J Cardiol :
Cannone, Valentina; Buglioni, Alessia; Sangaralingham, S Jeson et al. (2018) Aldosterone, Hypertension, and Antihypertensive Therapy: Insights From a General Population. Mayo Clin Proc 93:980-990
Fayyaz, Ahmed U; Edwards, William D; Maleszewski, Joseph J et al. (2018) Global Pulmonary Vascular Remodeling in Pulmonary Hypertension Associated With Heart Failure and Preserved or Reduced Ejection Fraction. Circulation 137:1796-1810
Kawakami, Rika; Lee, Candace Y W; Scott, Christopher et al. (2018) A Human Study to Evaluate Safety, Tolerability, and Cyclic GMP Activating Properties of Cenderitide in Subjects With Stable Chronic Heart Failure. Clin Pharmacol Ther 104:546-552
Saiki, Hirofumi; Petersen, Ivy A; Scott, Christopher G et al. (2017) Risk of Heart Failure With Preserved Ejection Fraction in Older Women After Contemporary Radiotherapy for Breast Cancer. Circulation 135:1388-1396
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:
Lee, Candace Y W; Huntley, Brenda K; McCormick, Daniel J et al. (2016) Cenderitide: structural requirements for the creation of a novel dual particulate guanylyl cyclase receptor agonist with renal-enhancing in vivo and ex vivo actions. Eur Heart J Cardiovasc Pharmacother 2:98-105
Wan, Siu-Hin; Stevens, Susanna R; Borlaug, Barry A et al. (2016) Differential Response to Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Reduced or Preserved Ejection Fraction: Results From the ROSE AHF Trial (Renal Optimization Strategies Evaluation in Acute Heart Failure). Circ Heart Fail 9:
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:
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

Showing the most recent 10 out of 124 publications