Recent evidence of a potential role for cardiac progenitor cells (CPCs) in cardiac repair and the discovery of a vasoprotective axis of the renin-angiotensin system (RAS) offer such breakthroughs. Investigators have observed that an imbalance in the vasoprotective axis {angiotensin converting enzyme 2 (ACE2)/angiotensin-(1-7) \[Ang-(1-7)\]/Mas receptor} and the vasodeleterious axis \[angiotensin converting enzyme (ACE)/angiotensin II (AngII)/AngII type 1 receptor (AT1R)\] of the RAS within the CPCs affects their functionality and regenerative potential. Investigators believe that restoring the balance between these two axes of the RAS is essential to improve CPC function and enhance their reparative capabilities. These observations have led to the hypothesis that genetic modification of CPCs by overexpression of ACE2/Ang-(1-7) will enhance their reparative function and improve their potential to attenuate myocardial ischemia-induced cardiac damage.
As a participant undergoes a clinically indicated heart transplant, or a left ventricular assist device (LVAD) implantation, or a right heart biopsy, or atrial fibrillation surgery, or right atria cannulation, the following tissue samples will be collected: In the subjects undergoing orthotopic heart transplant (n=20), failed myocardial tissue samples will be collected from the diseased heart. For subjects undergoing left ventricular assist device implantation (n=60), small samples will be collected from the apex core (that would be routinely discarded at the time of the implantation procedure). For heart transplant subjects undergoing clinically indicated right heart biopsy (n=20), the collection of multiple samples including, excess myocardial biopsy samples that will not be utilized by pathology. For subjects undergoing any heart surgery (n=80), the collection of left atrial appendages that are routinely removed to prevent thrombosis during atrial fibrillation surgery and a piece of the right atria will be cut in order to implant the cannula. In addition, a collection of 20ml (about one tablespoon) of blood will be taken from all subjects to analyze progenitor/inflammatory cells and inflammation cytokines and pertinent medical history.
Study Type
OBSERVATIONAL
Enrollment
8
Small samples collected from the apex core in the heart. In addition, blood samples will be taken.
Heart samples collected including, excess myocardial biopsy samples. In addition, blood samples will be taken.
Myocardial tissue samples collected from the diseased heart. In addition, blood samples will be taken.
Heart samples will be collected from the left atrial appendages. In addition, blood samples will be taken.
All subjects will have 20 ml of blood drawn for further analysis.
Yanfei Qi
Gainesville, Florida, United States
Imbalance of vasoprotective and vasodeleterious axes of the renin angiotensin system (RAS) is associated with dysfunction of CPC isolated from diseased tissue
CPCs will be isolated from the collected heart tissue. Function assay such as proliferation, migration, reactive oxygen species (ROS) level will be analyzed. Renin-angiotensin system (RAS) genes and inflammatory cytokines will be quantifies using polymerase chain reaction (PCR) and protein assay to investigate if the cell dysfunction is associated with the imbalance of vasoprotective and vasodeleterious axes of the RAS.
Time frame: two years
Screening for biomarkers related to clinic outcome in the blood
Progenitor/inflammatory cells, inflammatory cytokines, and growth factors will be measured to determine if they are associated with heart diseases.
Time frame: two years
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