Role of Exosomes Derived From Epicardial Fat in Atrial Fibrillation

Exosome plays an important role in the pathophysiology of the cardiovascular system. Since the field of cardiovascular exosome is still in its infancy, there are no available data regarding to its role in cardiac arrhythmias. The current study investigates the role of epicardial fat derived exosomes in patients who suffer from atrial fibrillation.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Epicardial fat biopsy

Detailed Description

Myocardial cells communication is mediated via direct cell to cell contact, cell to matrix interaction, long-range signals, electrical signals, and via extracellular chemical molecules (such as proteins, nucleotides, lipids and short peptides). Cell to cell communication can be achieved through direct contact (i.e. Gap junction, cell surface protein/protein interaction) or via secreted signaling molecules (i.e. hormones, neurotransmitters, cytokines). In the last few decades, a third intercellular communication mechanism has gained intense attention - extracellular vesicles that include: (1) apoptotic vesicles (1000-4000 nm), (2) microvesicles (100 nm - 1000 nm), and the smallest extracellular vesicles (3) exosomes (40-100 nm).

The exosomes are produced through the endosomal pathway and are able to carry cargo and transfer them to recipient cells, thus contributing to cell-to-cell communication. The exosomes cargo includes protein content, rRNA, tRNA, short DNA sequences, messenger RNA (mRNA) and microRNA (miRNA). The last two can change the gene expression within the target cells and by that affect myocardial cells.

Nowadays, it is known that in the cardiovascular system, exosome plays important roles in the pathophysiology of myocardial infarction (MI) and as an indicator for the damage and repair mechanisms post-acute MI (i.e. miR-126), in myocardial remodeling, and cardiac regeneration.

Since the field of cardiovascular exosome is still in its infancy, there are no available data regarding to its role in cardiac arrhythmias. Therefore, there is place to investigate the role of exosomes in patients who suffer from atrial fibrillation.

Some of the important issues to explore are: (1) Do the epicardial fat in patients with atrial fibrillation release quantitatively and qualitatively different exosomes than in patients without atrial fibrillation? (2) Can epicardial fat exosomes be a clinical biomarker for arrhythmias? (3) Can these exosomes be a target for the treatment and prevention of arrhythmias?

The current study will include patients who undergo any cardiac surgery and will give informed consent. An epicardial fat biopsy will be taken and cultured in a medium that contain M-199 medium, dexamethasone, gentamicin, and insulin for 9 days. The exosomes will be collected from the medium and analyzed.

The participants will be divided into two groups: (1) participants with atrial fibrillation, (2) participants who did not develop ever atrial fibrillation.

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dina Kogan; Phone Number: 972-52-8646402; Email: Diana.Kogan@sheba.health.gov.il

Study Locations

• Israel
  • Ramat Gan, Israel, 52621
    • Recruiting
    • Sheba Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• Undergoing an elective cardiac surgery

Exclusion Criteria:

• Undergoing a non-elective surgery
• Suffering from severe renal impairment prior to surgery (creatinine clearance <30 mL/min)
• Experienced hepatic dysfunction other than mild

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Atrial fibrillation; An epicardial fat biopsy will be taken from patients with chronic atrial fibrillation or paroxysmal atrial fibrillation who undergo any cardiac surgery	Procedure: Epicardial fat biopsy; A 1 cm (~0.5 g) of epicardial pat biopsy from the area of the pulmonary artery
OTHER: Control; An epicardial fat biopsy will be taken from patients without any history of atrial fibrillation who undergo any cardiac surgery	Procedure: Epicardial fat biopsy; A 1 cm (~0.5 g) of epicardial pat biopsy from the area of the pulmonary artery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exosomes quantity excreted from the epicardial fat (nm)	The differences in the quantity of exosomes derived epicardial fat in patients with and without atrial fibrillation. The exosome isolation will be done by using ultra centrifuge for cells and cells debris removal. Then the exosomes will examined by the Malvern NanoSight device both for particle size and concentration measurement.	9 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory cytokines secretion from epicardial fat	The differences in the Inflammatory cytokines secreted from epicardial fat in patients with and without atrial fibrillation. The investigators will detect the levels of cytokines and acute phase proteins such as IL1, IL2, IL6, IL8, IL10, IL12, CRP, VEGF, TNF-a, and TGF by Human Cytokine Array Kit.	9 days

Collaborators and Investigators

• Sponsor: Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 21, 2018
• Primary Completion (ANTICIPATED): January 21, 2022
• Study Completion (ANTICIPATED): January 21, 2022

Study Registration Dates

• First Submitted: March 20, 2018
• First Submitted That Met QC Criteria: March 23, 2018
• First Posted (ACTUAL): March 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Epicardial fat
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: SHEBA-18-4516-ER-CTIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Results: The exosomes content in patients with and without atrial fibrillation

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No