The overall objective of this resubmitted project remains focused on the establishment of a cell based technique to prevent progressive left ventricular (LV) dysfunction in a dog model of heart failure using an intracoronary infusion of genetically-modified autologous blood outgrowth endothelial cells that express brain natriuretic peptide (BNP). The natriuretic peptide system (NPS) plays an important physiological role in the humoral integration of the heart, kidney and vasculature to control sodium balance and arterial blood pressure, and there is emerging evidence that activation of this system is beneficial. Specifically, it is considered a compensatory endocrine response to LV dysfunction that maintains sodium balance without activating the renin-angiotensin-aldosterone system and increasing filling pressure. Presently, BNP has been approved for IV use in heart failure and there are clinical trials that are being conducted in Europe to investigate the therapeutic role of endothelial progenitor cells (EPCs) in myocardial ischemia and in nonischemic left ventricular (LV) dysfunction. Thus this application?s significance is that it addresses an important clinical problem using a promising cellular and genetic approach.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL076611-02
Application #
7674282
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
2
Fiscal Year
2006
Total Cost
$418,697
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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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

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