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Cardiovascular Research Laboratory
Harrison Department of Surgical Research
Y. Joseph Woo, M.D.

Basic Science Research

Areas of Study
Selected Publications:
Jayasankar V, Pirolli TJ, Bish LT, Berry MF, Burdick J, Grand T, Woo YJ. Targeted overexpression of growth hormone by adenoviral gene transfer preserves myocardial function and ventricular geometry in ischemic cardiomyopathy. J Molec Cell Cardiol 2004;36:531-538. (PDF)
Berry MF, Pirolli TJ, Jayasankar V, Morine KJ, Moise MA, Fisher O, Gardner TJ, Patterson PH, Woo YJ. Targeted overexpression of leukemia inhibitory factor preserves myocardium in postinfarction heart failure. J Thoracic and Cardiovasc Surg 2004;128:866-875. (PDF)

Cardiovascular disease is a major global health concern. The American Heart Association’s 2006 update reported cardiovascular disease as the number one cause of mortality in the USA accounting for 37% of all deaths. Nearly 7.2 million Americans have sustained a myocardial infarction (MI). With an increase in obesity, physical inactivity, and an aging population, the incidence of cardiovascular disease related morbidity and mortality is expected to increase dramatically.

An acute myocardial infarction, particularly one that is large and transmural, can produce alterations in the topography of both the infarcted and noninfarcted regions of the ventricle. This adverse remodeling is influenced by three interdependent factors: infarct size, infarct healing, and ventricular wall stresses, and negatively impacts the function of the ventricle and the prognosis for survival. There has been significant interest in infarct modulation and myocardial structural preservation to prevent these adverse outcomes. Clinical therapies include pharmacology, percutaneous and surgical revascularization, mechanical restraints and surgical resections which attempt to improve myocardial efficiency and function by restoring ventricular geometry. Unfortunately, most therapies are instituted relatively late in the overall time course of the disease process.


Our lab focuses on novel, alternative strategies for the treatment of ischemic cardiomyopathy. Strategies we have successfully used in the past include the regulation of apoptosis, myocardial ischemia protection, and somatotropism. We are currently exploring three main strategies for cardiac repair: Angiogenesis, Myocardial Regeneration, and Tissue Engineering.

Angiogenesis: In myocardial infarction, cardiomyocyte death occurs as a result of inadequate vascular supply. One approach to limit cell death in ischemic heart disease is to stimulate the growth of a new microcirculation to augment tissue perfusion in the setting of myocardial infarction.

Two angiogenic strategies we are currently exploring utilize Endothelial Progenitor Cells (EPCs). The first approach is to utilize the body’s endogenous machinery for angiogenesis. When stimulated appropriately with naturally-occurring cytokines, the production of EPCs can be significantly amplified, and then targeted to the ischemic zone of the myocardium. The second strategy is to harvest EPCs from the blood and/or bone marrow, isolate, purify, and propagate the cells in vitro, and then deliver cells to the the relatively ischemic borderzone of a myocardial infarction.

Woo YJ, Grand TJ, Berry MF, Atluri A, Moise MA, Hsu V, Cohen J, Fisher O, Pirolli T, Burdick J, Taylor M, Zentko S, Jayasankar V, Gardner TJ, Sweeney HL. Stromal cell-derived factor and granulocyte monocyte colony stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy. J Thoracic and Cardiovasc Surg 2005;130:321-329. (PDF)
Representative images of myocardial section depicting vWF-expressing blood vessels (green) for control
A.) Saline treated and B.) SDF/GM-CSF treated animals.

Myocardial Regeneration: The traditional belief that the adult mammalian heart is a terminally differentiated organ without regenerative potential has been challenged in recent years. It is now evident that the heart possesses the capacity for self-repair following injury. Unfortunately, these mechanisms are inadequate to compensate for the extensive damage which occurs in myocardial infarction.

We are actively exploring two approaches to myocardial regeneration therapy for heart failure. Modulation of cell cycle regulation offers an attractive approach to induce quiescent cardiomyocytes to re-enter the cell cycle and undergo mitosis, thereby increasing the number of functional cardiomyocytes. Cardiac Stem Cells (CSCs) offer an alternative approach. Recently discovered is a resident cardiac population of putative stem cells with endothelial, smooth muscle, and striated muscle potential. These have been referred to as Cardiac Stem Cells, and offer a promising avenue for cardiac repair following ischemic injury.

Woo YJ, Panlilio CM, Cheng RK, Liao GP, Atluri P, Cohen JE, Chaudhry HW. Therapeutic delivery of cyclin A2 induces myocardial regeneration and enhances cardiac function in ischemic heart failure. Circulation 2006;114:206-213. (PDF)
Control Heart following LAD ligation and development of ischemic heart failure. Alpha sarcomeric actin appears red; DAPI stained nuclei appear blue. Phosphohistone H3, a marker of mitosis, if present, would appear green. Cyclin A2 treated heart showing active intranuclear mitosis. Phosphohistone H3 appears green, Alpha sarcomeric actin appears red, and DAPI stained nuclei appear blue.
Tissue Engineering: Tissue engineering as a method of cardiac repair is an exciting area of research in the treatment of cardiovascular diseases. It has translational potential in the treatment of infarction, valvular heart disease, and end-stage heart failure. We are currently exploring methods of creating bioengineered sheets of beating cardiomyocytes for experimental implantation into animal models of ischemic cardiomyopathy.


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