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 #
5R01HL095874-03
Application #
8045345
Study Section
Cardiac Contractility, Hypertrophy, and Failure Study Section (CCHF)
Program Officer
Mcdonald, Cheryl
Project Start
2009-04-15
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
3
Fiscal Year
2011
Total Cost
$381,250
Indirect Cost
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
Gupta, Rajesh; Mackie, Alexander R; Misener, Sol et al. (2018) Endothelial smoothened-dependent hedgehog signaling is not required for sonic hedgehog induced angiogenesis or ischemic tissue repair. Lab Invest 98:682-691
Morishita, Yoshihiro; Kobayashi, Koichi; Klyachko, Ekaterina et al. (2016) Wnt11 Gene Therapy with Adeno-associated Virus 9 Improves Recovery from Myocardial Infarction by Modulating the Inflammatory Response. Sci Rep 6:21705
Jeyabal, Prince; Thandavarayan, Rajarajan A; Joladarashi, Darukeshwara et al. (2016) MicroRNA-9 inhibits hyperglycemia-induced pyroptosis in human ventricular cardiomyocytes by targeting ELAVL1. Biochem Biophys Res Commun 471:423-9
Joladarashi, Darukeshwara; Garikipati, Venkata Naga Srikanth; Thandavarayan, Rajarajan A et al. (2015) Enhanced Cardiac Regenerative Ability of Stem Cells After Ischemia-Reperfusion Injury: Role of Human CD34+ Cells Deficient in MicroRNA-377. J Am Coll Cardiol 66:2214-2226
Khan, Mohsin; Nickoloff, Emily; Abramova, Tatiana et al. (2015) Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction. Circ Res 117:52-64
Tongers, Jörn; Webber, Matthew J; Vaughan, Erin E et al. (2014) Enhanced potency of cell-based therapy for ischemic tissue repair using an injectable bioactive epitope presenting nanofiber support matrix. J Mol Cell Cardiol 74:231-9
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
Sekiguchi, Haruki; Ii, Masaaki; Jujo, Kentaro et al. (2013) Estradiol promotes neural stem cell differentiation into endothelial lineage and angiogenesis in injured peripheral nerve. Angiogenesis 16:45-58
Mackie, Alexander R; Krishnamurthy, Prasanna; Verma, Suresh K et al. (2013) Alcohol consumption negates estrogen-mediated myocardial repair in ovariectomized mice by inhibiting endothelial progenitor cell mobilization and function. J Biol Chem 288:18022-34
Raval, Zankhana; Losordo, Douglas W (2013) Cell therapy of peripheral arterial disease: from experimental findings to clinical trials. Circ Res 112:1288-302

Showing the most recent 10 out of 47 publications