Before consideration for transplant or LVAD insertion, patients with congestive heart failure (CHF) are optimized in medical treatment and, if the left ventricular dysfunction is secondary to ischemia, revascularization, consisting of bypass surgery and/or percutaneous intervention, may be performed if feasible. The rationale for considering revascularization in the setting of CHF is based on the concept of hibernating myocardium, i.e. viable myocardium that is hypo-contractile due to hypoperfusion. Our laboratory has been pursuing the concept of microvascular repair as a means of improving symptoms and function in patients with ischemic disease. These efforts have included the application of angiogenic factors and cell based strategies in an attempt to leverage naturally occurring mechanisms for tissue repair. The present proposal is an extension of prior work in our lab and a continuation of our long-standing goal to define mechanisms of ischemic tissue repair and develop novel therapeutics based on these discoveries. If successful the experiments outlined in this proposal could identify novel therapeutics to improve blood flow and function in patients with congestive heart failure.

Public Health Relevance

This proposal is an extension of prior work in our lab and a continuation of our long-standing goal to define mechanisms of ischemic tissue repair and to identify and develop novel therapeutics to improve blood flow and function in patients with congestive heart failure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL095874-04
Application #
8240906
Study Section
Cardiac Contractility, Hypertrophy, and Failure Study Section (CCHF)
Program Officer
Mcdonald, Cheryl
Project Start
2009-04-15
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$377,438
Indirect Cost
$129,938
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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Ghosh, Asish K; Murphy, Sheila B; Kishore, Raj et al. (2013) Global gene expression profiling in PAI-1 knockout murine heart and kidney: molecular basis of cardiac-selective fibrosis. PLoS One 8:e63825
Jujo, Kentaro; Ii, Masaaki; Sekiguchi, Haruki et al. (2013) CXC-chemokine receptor 4 antagonist AMD3100 promotes cardiac functional recovery after ischemia/reperfusion injury via endothelial nitric oxide synthase-dependent mechanism. Circulation 127:63-73
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Zhou, Junlan; Cheng, Min; Wu, Min et al. (2013) Contrasting roles of E2F2 and E2F3 in endothelial cell growth and ischemic angiogenesis. J Mol Cell Cardiol 60:68-71
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Kishore, Raj; Verma, Suresh K; Mackie, Alexander R et al. (2013) Bone marrow progenitor cell therapy-mediated paracrine regulation of cardiac miRNA-155 modulates fibrotic response in diabetic hearts. PLoS One 8:e60161
Sekiguchi, Haruki; Ii, Masaaki; Jujo, Kentaro et al. (2012) Estradiol triggers sonic-hedgehog-induced angiogenesis during peripheral nerve regeneration by downregulating hedgehog-interacting protein. Lab Invest 92:532-42
Nishimura, Yukihide; Ii, Masaaki; Qin, Gangjian et al. (2012) CXCR4 antagonist AMD3100 accelerates impaired wound healing in diabetic mice. J Invest Dermatol 132:711-20
Gupta, Rajesh; Losordo, Douglas W (2011) Cell therapy for critical limb ischemia: moving forward one step at a time. Circ Cardiovasc Interv 4:2-5

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