Cardiovascular Disease Protection Tissue

Effects of ACE2/Ang-(1-7) on Cardiac Progenitor Cells From Heart Failure Patients and Explant Control

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Ischemia
• Intervention / Treatment: Procedure: Heart failure or coronary disease; Procedure: Blood Draw; Procedure: Heart transplant patients; Procedure: Orthotopic Heart Transplant Patients; Procedure: Heart Surgery Patients

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.

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Yanfei Qi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing orthotopic heart transplant, left ventricular assist device implantation, right heart biopsy, and any other heart surgery (atrial fibrillation and right atria cannulation).

Description

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 exclusion criteria for this study.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Heart failure or coronary disease; This group will have small samples collected from the apex core (that would be routinely discarded at the time of the implantation procedure) by undergoing a left ventricular assist device implantation. In addition, a blood sample will be collected.	Procedure: Heart failure or coronary disease; Small samples collected from the apex core in the heart. In addition, blood samples will be taken.; Procedure: Blood Draw; All subjects will have 20 ml of blood drawn for further analysis.
Heart transplant patients; This group will have multiple samples collected including, excess myocardial biopsy samples that will not be utilized by pathology. In addition, a blood sample will be collected.	Procedure: Blood Draw; All subjects will have 20 ml of blood drawn for further analysis.; Procedure: Heart transplant patients; Heart samples collected including, excess myocardial biopsy samples. In addition, blood samples will be taken.
Orthotopic Heart Transplant Patients; This group will have myocardial tissue samples collected from the diseased heart. In addition, a blood sample will be taken.	Procedure: Blood Draw; All subjects will have 20 ml of blood drawn for further analysis.; Procedure: Orthotopic Heart Transplant Patients; Myocardial tissue samples collected from the diseased heart. In addition, blood samples will be taken.
Heart Surgery Patients; This groups will have samples collected from the 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 blood sample will be taken.	Procedure: Blood Draw; All subjects will have 20 ml of blood drawn for further analysis.; Procedure: Heart Surgery Patients; Heart samples will be collected from the left atrial appendages. In addition, blood samples will be taken.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	two years

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): September 28, 2018
• Study Completion (Actual): September 28, 2018

Study Registration Dates

• First Submitted: January 22, 2015
• First Submitted That Met QC Criteria: January 22, 2015
• First Posted (Estimate): January 28, 2015

Study Record Updates

• Last Update Posted (Actual): November 27, 2018
• Last Update Submitted That Met QC Criteria: November 23, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Ischemia; Ischemia
• Other Study ID Numbers: IRB201300122-N; R01HL056921 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO