Mer-TK in Human Cardiac Cells

Detecting Soluble MER Levels After Myocardial Ischemia and Reperfusion Injury in Pediatric Patients

The relationship between the immune system and the myocardium after myocardial ischemia is an evolving field of research. Crosstalk occurs between macrophages and cardiac myocytes to promote cardio-protection and resolution of inflammation after myocardial ischemia and reperfusion injury (MI/R injury).

Myeloid-epithelial-reproductive tyrosine kinase (MerTK), a member of the TAM family of tyrosine kinase receptors (Tyro-Axl-MerTK), is a macrophage receptor that mediates efferocytosis, anti-inflammatory signaling, and resolution of inflammation. After MI/R injury, intact MerTK is necessary for the phagocytosis of dead cardiac myocytes and to promote anti-inflammatory signaling. Proteolytic cleavage of MerTK to its inactive form, soluble MER, restricts the capacity of macrophages to phagocytize dead cardiac myocytes and impairs MerTK-dependent anti-inflammatory signaling resulting in suppressive effects on cardiac remodeling and function.

The Thorp lab at Northwestern University has previously measured soluble MER levels in both adult mice and humans and found that soluble MER concentrations increase after MI/R injury. In adult MI patients, soluble MER was measured post coronary artery reperfusion and was found to be increased (average 3200 pg/mL compared to 1700 pg/mL) compared to controls with stable cardiovascular disease. Based on murine data, the lab further postulated that reperfusion injury may directly interfere with MerTK-dependent cardiac repair as reactive oxygen species formed during reperfusion injury induce proteolytic cleavage of MerTK to soluble MER.

Myocardial infarctions are rare events in pediatric patients. However, pediatric hearts are exposed to periods of hypoperfusion, ischemia, and inflammation during times of stress such as cardiac bypass and critical illness, and it is unknown how soluble MER levels change in response to these events. Thus, I was interested in investigating how soluble MER levels change after MI/R injury induced by cardiac bypass as well as in the utility of soluble MER as a biomarker of cardiac inflammation and injury in pediatric patients.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Myocardial Inflammation
• Intervention / Treatment: Other: Change in Soluble MER Concentration

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H Lurie Children's Hopsital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 19 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Pediatric patients with congenital heart disease presenting to Lurie Children's Hospital for corrective or palliative heart surgery and will be undergoing cardiac bypass.

Description

Inclusion Criteria:

• All patient ages from birth-19 years-old as well as cyanotic and acyanotic cardiac lesions will be included

Exclusion Criteria:

• Patients will be excluded if both pre and post bypass blood samples are not available.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pediatric Cardiac Bypass Patients; Blood samples obtained from patients ages from birth-19 years-old as well as cyanotic and acyanotic cardiac lesions who underwent cardiac bypass.	Other: Change in Soluble MER Concentration; Measuring change in soluble MER Concentration post compared to pre bypass for each patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Soluble MER Concentration	5/10/2019-12/31/2020

Secondary Outcome Measures

Outcome Measure	Time Frame
Utility of soluble MER as a biomarker of inflammation and injury	5/10/2019-12/31/2020

Collaborators and Investigators

• Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 10, 2019
• Primary Completion (ACTUAL): December 31, 2020
• Study Completion (ACTUAL): December 31, 2020

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (ACTUAL): March 26, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 12, 2021
• Last Update Submitted That Met QC Criteria: August 10, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cardiomyopathies; Myocardial Infarction; Infarction; Inflammation; Myocarditis
• Other Study ID Numbers: 2019-2445

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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