Myocardial Ischemia
Conditions
Brief summary
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.
Detailed description
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.
Interventions
PROCEDUREHeart failure or coronary disease
Small samples collected from the apex core in the heart. In addition, blood samples will be taken.
PROCEDUREHeart transplant patients
Heart samples collected including, excess myocardial biopsy samples. In addition, blood samples will be taken.
PROCEDUREOrthotopic Heart Transplant Patients
Myocardial tissue samples collected from the diseased heart. In addition, blood samples will be taken.
PROCEDUREHeart Surgery Patients
Heart samples will be collected from the left atrial appendages. In addition, blood samples will be taken.
PROCEDUREBlood Draw
All subjects will have 20 ml of blood drawn for further analysis.
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
University of Florida
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* heart transplant surgery * left ventricular assist device implantation * heart surgery required for atrial fibrillation and right atria cannulation
Exclusion criteria
* We are collecting discarded tissues following surgery. There is no
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Imbalance of vasoprotective and vasodeleterious axes of the renin angiotensin system (RAS) is associated with dysfunction of CPC isolated from diseased tissue | two years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Screening for biomarkers related to clinic outcome in the blood | two years | Progenitor/inflammatory cells, inflammatory cytokines, and growth factors will be measured to determine if they are associated with heart diseases. |
Countries
United States
Outcome results
None listed