Role of Exosomes Derived From Epicardial Fat in Atrial Fibrillation

NCT ID: NCT03478410

Last Updated: 2021-04-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-21
• Study Completion Date: 2022-01-21

Brief Summary

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.

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.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Atrial fibrillation

An epicardial fat biopsy will be taken from patients with chronic atrial fibrillation or paroxysmal atrial fibrillation who undergo any cardiac surgery

Group Type: OTHER

Epicardial fat biopsy

Intervention Type: PROCEDURE

A 1 cm (\~0.5 g) of epicardial pat biopsy from the area of the pulmonary artery

Control

An epicardial fat biopsy will be taken from patients without any history of atrial fibrillation who undergo any cardiac surgery

Group Type: OTHER

Epicardial fat biopsy

Intervention Type: PROCEDURE

A 1 cm (\~0.5 g) of epicardial pat biopsy from the area of the pulmonary artery

Interventions

Epicardial fat biopsy

A 1 cm (\~0.5 g) of epicardial pat biopsy from the area of the pulmonary artery

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sheba Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Dr. Eilon Ram

Resident in cardiac surgery, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eilon Ram, MD

Role: PRINCIPAL_INVESTIGATOR

Sheba Medical Center

Locations

Sheba medical center

Ramat Gan, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Eilon Ram, MD

Role: CONTACT

eilon.ram@sheba.health.gov.il

972-54-4929101

Dina Kogan

Role: CONTACT

Diana.Kogan@sheba.health.gov.il

972-52-8646402

Facility Contacts

Diana Kogan

Role: primary

Diana.Kogan@sheba.health.gov.il

972-52-8646402

Eilon ram, MD

Role: backup

eilon.ram@sheba.health.gov.il

972-54-4929101

Other Identifiers

SHEBA-18-4516-ER-CTIL

Identifier Type: -

Identifier Source: org_study_id