MYOCARDIAL NEOVASCULARIZATION FOR ISCHEMIC HEART DISEASE USING BONE MARROW-DERIVED ANGIOBLASTS [ 2003 - 2004 ]

Research Grant

Researchers: A/Pr Silviu Itescu (Principal investigator) ,  Prof Henry Krum

Brief description Congestive heart failure remains a major public health problem. In Western societies heart failure is primarily the consequence of a previous myocardial infarction. We have recently identified certain cells in the bone marrow of adult humans that can cause new blood vessel development in the heart after infarction, protecting the heart muscle cells against death and preventing heart failure. Since the cardiovascular diseases that are most likely to benefit from treatments utilizing adult bone marrow-derived endothelial progenitors, or angioblasts, predominantly affect aging individuals, critical questions that must be addressed are whether advanced age and-or progression of cardiovascular disease reduce the total numbers and-or the functional activity of such cells. In the current proposal we will investigate the relationship between increasing age or progression of ischemic heart disease and changes in the number and in vivo biologic properties of human angioblasts. Patients at various ages and stage of cardiovascular disease will be studied. Angioblast numbers will be quantitated in freshly obtained bone marrow cells. The ability of purified angioblasts to be targeted to the ischemic heart will be studied by labeling the angioblasts with a radioactive tracer and measuring tracer uptake in the heart at various time points after intravenous infusion of the cells. Finally, angioblast functional capacity will be evaluated using standard measurements of heart function before and at various time points after reinfusion of cells into the donor. In Aims 2 and 3 of this proposal we will focus our investigations on the potential use of angioblast therapy for reversal of established chronic heart failure in our animal models. Specifically, we will investigate whether induction of neovascularization results in cardiomyocyte regeneration and explore novel strategies to augment heart muscle regeneration by increasing angioblast trafficking to the damaged myocardium .

Funding Amount $AUD 577,400.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant