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Overview

Our research aims to use gene therapy to mobilize bone marrow stem cells and RNAi to chemoattract the progenitor cells to damaged heart tissue with the goal of treating ischemic cardiomyopathy.

Background Research

Ischemic cardiomyopathy

Ischemic cardiomyopathy is a cause of congestive heart failure due to coronary artery disease. Ischemic refers the condition in which an organ does not obtain sufficent oxygen. Myopathy refers to a muscle related disease. Ischemic cardiomypoathy affects approximately 1 of 100 people in the United States.

SDF-1α

SDF-1α is a chemokine responsible for attracting stem cells to the heart. SDF-1α is secreted from epithelial cells in ischemic tissue and inactivated by CD26/DPP-IV.

CD26/DPP-IV

CD26/DPP-IV (dipeptidylpeptidase IV) cleaves SDF-1α at its position 2 proline. DPP-IV is a memebrane bound extracellular peptidase.

CD26/DPP-IV

CXCR-4 is a homing receptor, expressed on many progenitor cells circulating in the blood. Active SDF-1α binds CXCR-4.

Resources

1. Zaruba, M-M. et al. "Synergy between CD26/DPP–IV inhibition and G–CSF improves cardiac function after acute myocardial infarction." Cell Stem Cell 4 313–323 (2009). http://www.ncbi.nlm.nih.gov/pubmed/19341621

1. “Ischemic cardiomyopathy.” Medical Encyclopedia. 3 September 2008 http://www.nlm.nih.gov/medlineplus/ency/article/000160.htm

1. "Performing RNAi Experiments in Animals." Applied Biosystems. http://www.ambion.com/techlib/tn/131/5.html